2018 News and Events
Dr. Alkes Price Promoted to Professor
On September 14th, 2018, current and former trainees joined Dr. Alkes Price to celebrate his promotion to professor with a dinner at Kashmir Restaurant on Newbury Street. Congratulations, Dr. Price!
Grants and Awards
In February 2018, Dr. Kathryn Penney was awarded an NIH grant R01CA227190 (converted to R37CA227190) “Comprehensive characterization of prostate stromal gene expression and association with lethal prostate cancer”
Wonil Chung, Omer Weissbrod and Margaux Hujoel were awarded as semifinalists for the Charles J. Epstein Trainee Award for Excellence in Human Genetic Research for the 2018 American Society of Human Genetics Conference in San Diego, California this October.
Zhaozhong Zhu was selected to present a poster presentation with top 10% reviewers’ score at the 2018 American Society of Human Genetics Conference in San Diego, California this October.
On 9/6/18, Carla Marquez Luna successfully defended her thesis. She is a member of Dr. Alkes Price’s group.
Departures and Transitions:
On 4/27/18, Emily Slade successfully defended her dissertation. She has started a tenure-track faculty position at the University of Kentucky.
2018 PGSG Summer Outing:
To beat the summer heat, a group from PGSG went to the Charles River Canoe and Kayak in Kendall Square.
Zhu, Z., Lee, P.H., Chaffin, M., Chung, W., …, Liang L., Shared Genetic Architecture between Asthma and Allergic Diseases: A Genome-Wide Cross Trait Analysis of 112,551 Individuals from UK Biobank. Nature Genetics, 50(6):857-864, 2018. PMID: 29785011. PMCID: PMC5980765.
Gusev A, Mancuso N, Won H, Kousi M, Finucane HK, Reshef Y,…Crawford GE, Geschwind DH, Katsanis N, Sullivan PF, Pasaniuc B, Price AL. (2018). Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50, 538-548. PMCID: 5942893
Finucane HK, Reshef Y, Anttila V, Slowikowski K, Gusev A, Byrnes A,…Buenrostro JD, Bernstein BE, Raychaudhuri S, McCarroll S, Neale BM, Price AL. (2018). Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat Genet 50, 621-629. PMCID: 5896795
Loh, PR, Kichaev G, Gazal S, Schoech AP, Price AL. (2018). Mixed-model association for biobank-scale datasets. Nat Genet 50, 906-908. PMCID in progress
Hormozdiari F, Gazal S, van de Geijn B, Finucane HK, Ju CJ, Loh PR, Schoech A, Reshef Y, Liu X, O’Connor L, Gusev A, Eskin E, Price AL. (2018). Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits. Nat Genet 50, 1041-1047. PMCID: 6030458
Loh PR*, Genovese G*, Handsaker RE, Finucane HK, Reshef YA, Palamara PF, Birmann BM, Talkowski ME, Bakhoum SF, McCarroll SA**, Price AL**. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. (2018) Nature 559, 350-355. PMCID: 6054542
Palamara P, Terhorst J, Song YS, Price AL. High-throughput inference of pairwise coalescence times identifies signals of selection and enriched disease heritability. (2018) Nat Genet 50, 1311-1317. PMCID in progress
Reshef Y, Finuncane H, Kelley D, Gusev A, Kotlair D, Ulirsch J…Gazal S, Palamara P, Pinello L, Patterson N, Adams RP, Price AL. (2018) Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk. Nat Genet. Epub Sep 3. PMCID in progress
Gazal S, Loh PR, Finucane H, Ganna A, Schoech A, Sunyaev S, Price AL. Low-frequency variant functional architectures reveal strength of negative selection across coding and non-coding annotations. (2018) Nat Genet.
O’Connor L, Price AL. Distinguishing genetic correlation from causation across 52 diseases and complex traits. (2018) Nat Genet.
2017 News and Events
Jihye Kim received an American Association for Cancer Research Scholar-in-Training Award for the work she will be presenting at the AACR Annual Meeting in Chicago, Absolute risk prediction models for pancreatic cancer. Dr. Kim is a PGSG postdoctoral fellow working with Peter Kraft at the Harvard T.H. Chan School of Public Health and Brian Wolpin at the Dana-Farber Cancer Institute.
On 09/13/17, NIH grant R01 MH101244 “Rare and common variants in complex disease” (4 PIs: Sunyaev/Price/Kraft/Neale) was awarded to Alkes Price as a subcontract with BWH (Shamil Sunyaev)/NIMH.
Alkes Price received the 2017 Harvard Chan Outstanding Postdoctoral Mentor Award.
On 06/05/17, NIH grant R21 HG009513 (PI: Price) “Fast and accurate phasing using the positional Burrows-Wheeler transform (PBWT)” was awarded to Alkes Price.
On 05/03/17, NIH grant renewal R01 HG006399 (PI: Price) “Methods for disease mapping in multi-ethnic populations” was awarded to Alkes Price.
On 02/01/17, NIH grant U01 HG009379 (PIs: Price/Raychaudhuri) “Functionally specialized components of disease heritability in ENCODE data” was awarded to Alkes Price.
Peter Kraft’s project “Integrative approaches for mapping the genetic risk of complex traits” awarded as a subcontract with UCLA (Bogdan Pasanuic)/NHGRI.
Through an NIA R01 grant, Lori Chibnik will be the PI of a sub-contract entitled African Ancestry and the Genomic Architecture of AD and Other Common Neurodegenerative Disease Neuropathologies. The overall goal of Study of Ancestry and Neurodegenerative Diseases (SANDS) is to identify genomic variants of African and European Ancestry associated with AD and other common neurodegenerative disease pathologies, including: cerebrovascular disease, Lewy body disease, TDP-43, and hippocampal sclerosis. They are aiming to collect samples from 10,000 autopsies over a 5 year period.
Richard Barfield defended his PhD Biostatistics thesis (co-mentored by Peter Kraft and Xihong Lin): “Statistical Methods for Analysis of Genetic and Genomic Data in Population Science.” Richard started a postdoctoral fellowship at the Fred Hutchison Cancer Research Center.
Anne Feng defended her ScD Epidemiology thesis (mentored by Liming Liang): “Statistical Analysis and Methods for Human Omics Data”. Anne started a postdoctoral fellowship with Ben Neale at the Analytic and Translational Genetics Unit at Massachusetts General Hospital.
Helian Feng presented her Master’s thesis (mentored by Peter Kraft): “A Transcriptome-Wide Association Study of Breast Cancer.” Helian started the PhD Biostats program at HSPH.
Natalie DuPre defended her thesis: “Air Pollution in Relation to Mammographic Density, Breast Cancer Survival, and Breast Tissue Gene Expression” (Mentored by Rulla Tamimi). She will continue on as a postdoctoral fellow in the Epidemiology Department at HSPH.
Abhinav Reddy presented his Master’s thesis (mentored by Liming Liang): “Multi-Tissue eQTL Analysis and Cross-Tissue Heritability Weighting in Cornonary Artery Disease.”
Kevin Galinsky defended his PhD thesis “Biological insights from population differentiation” on 01/25/17.
Hilary Finucane defended her PhD thesis “Functional and cross-trait genetic architecture of common diseases and complex traits” on 04/28/17.
In January 2017, former PGSG post-doc Sasha Gusev from Alkes Price’s group started a tenure-track faculty position at DFCI/Harvard Medical School.
In June 2017, PGSG doctoral student Hilary Finucane from Alkes Price’s group started a Broad Fellow/PI position at the Broad Institute.
In July 2017, PGSG post-doc Pier Palamara from Alkes Price’s group started a tenure-track Associate Professor position at the University of Oxford.
In August 2017, PGSG post-doc Po-Ru Loh from Alkes Price’s group started a tenure-track faculty position at BWH/Harvard Medical School
2015-2016 News and Events
Dr. Liming Liang, Associate Professor of Statistical Genetics, led the organization of the first Youth in Public Health Symposium in China, together with the Office of Diversity and Inclusion and the Postdoc Association at the Harvard Chan School. The symposium took place at Harvard Center Shanghai between August 24-26, 2016, and aimed to provide Chinese youth with exposure to the range of areas within the field of public health, skills to develop research questions, and resources and a network of colleagues within the field of public health. The 3-day symposium leveraging the existing Public Health 101 nanocourse series at the school was very well received by a total of 71 high school students from top high schools across the country. According to a survey based on 66 questionnaires, more than 83% of the students would be more likely to pursue public health as a career or education after the symposium. More information can be found on the course website, as well as the HSPH featured news website.
Numerous PGSGers are presenting their work at the upcoming ASHG and IGES meetings in October 2016. Doctoral student Richard Barfield’s IGES presentation is nominated for a Williams Award (Best Student Presentation). Kevin Galinsky’s platform talk was selected for a 2016 ASHG/Charles J. Epstein Research Finalist Award.
In addition, Anne Feng and Hilary Finucane both had their ASHG posters selected as a Reviewer’s Choice (in the top 10% of abstracts).
To see the full list of talks and posters click here.
Congratulations to David Hunter and Peter Kraft for being in the top 1% of Highly Cited Researchers list by Clarivate Analytics for 2016. This distinction is given to those who are the most highly cited researchers in their fields. http://hcr.stateofinnovation.com
Peter Kraft’s project “Circulating Biomarker Consortium for Pancreatic Cancer Early Detection” was awarded by the NIH/NCI via Dana-Farber Cancer Institute. The project period is August 1, 2016 – July 31, 2021.
Congratulations to Alkes Price, who received the NSF CAREER Award for his work on “Resources for mixed model association mapping of complex traits.” The CAREER program is one of the National Science Foundation’s most prestigious awards; it supports junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organizations.
Peter Kraft, David Hunter, and Sara Lindstroem are authors on a new paper out in JNCI in April 2015 that identifies new genetic markers of breast cancer survival. Survival after diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. This research is currently the largest study investigating genetic variation associated with breast cancer survival. The full article can be read here.
Liming Liang is first author of a new EWAS study published in Nature, “An epigenome-wide association study of total serum immunoglobulin E concentration,” featured on the HSPH news website. The researchers have discovered more than 30 genes that have strong effects on Immunoglobulin E (IgE- the antibody that triggers allergic responses), allergies and asthma. Amongst the genes are promising novel drug targets for treating allergies and asthma. The full article can be read here.
Immaculata De Vivo and collaborators have a paper just out in JAMA which found that patients who receive bone marrow transplants from donors with longer telomeres have a higher probability of survival over a 5-year period. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term post-transplant survival. Read the full article here.
Alkes Price is featured in the HSPH News for his recent work on “Leveraging population admixture to characterize the heritability of complex traits,” published in Nature Genetics. Read the full profile here.
Immaculata De Vivo and Marta Crous Bou have a new paper featured in the December edition of the British Medical Journal. Their work examines genetic factors that may contribute to the link between the Mediterranean diet and longer telomeres, using data from the Nurses’ Health Study. The full editorial can be read here.
PGSGers have had an impressive number of papers published recently in high-impact journals. Sara Lindström and Rulla Tamimi are first and last authors on a new paper in Nature Communications that identified multiple loci associated with both mammographic density and breast cancer risk; Price lab members have a new paper, “Leveraging population admixture to characterize the heritability of complex traits,” published in Nature Genetics; Postdoc Gaurav Bhatia had his paper on directional selection in African-Americans published in AJHG; Amit Joshi and Peter Kraft are first and last authors on their work published in the American Journal of Epidemiology examining additive interactions and breast cancer risk; “Variation in Predictive Ability of Common Genetic Variants by Established Strata: The Example of Breast Cancer and Age,” now published in Epidemiology, has an all-PGSG author list, led by Hugo Aschard; Jennifer Prescott is first author on a paper recently published in Frontiers in Oncology analyzing Vitamin D and ovarian cancer risk; Postdoc Sasha Gusev’s work on “Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases” was published in AJHG; Liming Liang is first author of a paper in press at Nature, “An Epigenome-Wide Association Study of Total Serum Immunoglobulin E Concentration” and co-first author of a paper in press at Human Molecular Genetics, “Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci”; Marta Crous Bou and Immaculata De Vivo’s paper, “Mediterranean diet and telomere length in the Nurses’ Health Study: Population-based cohort study,” is in press at BMJ; and postdoc Po-Ru Loh just had his paper on Bayesian mixed model analysis accepted in Nature Genetics.
Rulla Tamimi is Co-PI on a new grant funded by Susan G. Komen for the Cure. The study, “Environmental exposures, early proliferative changes and breast cancer risk,” will evaluate if environmental exposures and geographic variation over the life course are related to mammographic density, proliferative BBD and breast cancer risk, independent of individual level risk factors. In addition, it also examines the associations of air pollution and UV-B with gene expression in normal (benign) breast tissue. Dr. Tamimi will be working with Co-PI Francince Laden, Associate Professor of Epidemiology and Environmental Health at HSPH.
Alkes Price and Peter Kraft, in collaboration with Ben Neale and Shamil Sunyaev of the Broad Institute, received an R01 to develop statistical methods for studies of rare variants.
Liming Liang promoted to Associate Professor
Congratulations to Dr. Liming Liang, who was promoted to Associate Professor in the Fall of 2015. Dr. Liang has been with PGSG since 2009. His research focuses primarily on developing the computational and statistical tools required for understanding human genetic variation, with a particular focus on complex human disease.
Hugues Aschard promoted to Research Scientist
Congratulations to Dr. Hugo Aschard, who was promoted from Research Associate to Research Scientist in Fall 2015. Dr. Aschard has been at HSPH since 2010, when he began his postdoc with PGSG Director Peter Kraft. His research explores computational and statistical methods to decipher the genetic architecture of multifactorial traits, with an emphasis on integrative analysis of biological, clinical and environmental data and the evaluation of their potential interactions.
Peter Kraft is co-author on a recently published paper in Nature, “Directional dominance on stature and cognition in diverse human populations.” The study examined runs of homozygosity of 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and found statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment. The full article can be accessed here.
A new paper on “Modeling linkage disequilibrium increases accuracy of polygenic risk scores” has been accepted by AJHG. Led by former PGSG postdoc Bjarni Vilhjalmsson, this work introduces a new method of calculating polygenic risk scores, LDpred, which infers the posterior mean effect size of each marker using a prior on effect sizes and LD information from an external reference panel. Numerous PGSGers, past and present, were closely involved in this work.
Over a dozen PGSGers have been selected to present their work at this year’s ASHG conference in Baltimore. In addition, postdoc Sasha Gusev has been selected as a finalist for the ASHG Epstein Trainee Award for Excellence in Human Genetics Research; and Gaurav Bhatia, Pier Palamara, Po-Ru Loh and doctoral students Kevin Galinsky and Tris Hayeck were all selected as semi-finalists. Click here to see detailed talk and poster information. Congratulations to all!
Two papers written by Price lab members have recently been accepted by Nature Genetics. Finucane et al., in press, is titled “Partitioning heritability by functional category using GWAS summary statistics”; and Bulik-Sullivan et al. in press, is written on “An atlas of genetic correlations across human diseases and traits.”
Congratulations to Drs. Akweley Ablorh, Alexis Carere, Zhonghua Liu, and Shasha Meng, who all graduated and received their doctoral degrees today after years of hard work. We know they will continue to do great research in the future and we wish them the best of luck.
Jennifer Prescott, who has worked with Dr. De Vivo for several years as a research fellow and now an instructor, was awarded a new grant from the Harvard Transdisciplinary Research on Energetics and Cancer (TREC) Center. The title of the project is “Influence of a family history of Type 2 Diabetes on colorectal cancer risk and mortality, and on biomarkers of glycemic control, plasma lipids, and inflammatory biomarkers.” The researchers hypothesize that increased insulin signaling increases the risk of colorectal cancer, based on previous studies that have shown healthy first-degree relatives of type 2 diabetics to have reduced insulin secretion due to impaired beta-cell function. The project will explore whether a family history of type 2 diabetes is associated with reduced risk of colorectal cancer incidence and mortality, and/or alters biomarkers associated with insulin action in the NHS and HPFS cohorts. Dr. Prescott will also explore whether a genetic risk score for type 2 diabetes is associated with colorectal cancer risk.
Postdoctoral fellow Amit Joshi also received grant funding from the TREC Center. Dr. Joshi’s research project is entitled “Effect modification of association of GWAS-identified susceptibility SNPs for body mass index with post-menopausal breast cancer risk by physical activity.” He will use data from the Nurses’ Health Study, which is one of the largest and longest running investigations of factors that influence women’s health.
Dr. Hugues Aschard, postdoctoral fellow under Dr. Kraft, was recently awarded grant 1R03HG006720-01A1, “Relaxing genetic models to identify genetic variants involved in gene-gene and gene-environment interactions.” Dr. Aschard and his colleagues developed a non-parametric test of association that compares phenotypic distribution by genotypic classes, which aims to identify quantitative trait loci involved in interactions. The aims of his grant are to identify potential technical improvements of the proposed method and to conduct real data application to identify genetic variants that have been missed by standard genome-wide association screening.
Po-Ru Loh received a PQG Student/Postdoc Travel Award to attend the Fall 2014 ASHG conference. The awards are funded by HSPH’s Program in Quantitative Genomics and are used to support travel to present research at professional meetings. In addition, Po-Ru has been selected as a semi-finalist for the 2014 ASHG Charles J. Epstein Trainee Award, for his work on “Efficient Bayesian mixed model analysis increases association power in large cohorts.”
Alexis Carere has received a Doctoral Foreign Study Award from the Canadian Institutes of Health Research. Dr. Peter Kraft and Dr. Robert Green co-supervise her project, titled, “A prospective cohort of direct-to-consumer genetic testing customers: Consumer motivations, behavioral responses, and their impact on the health care system.”
Postdoc Sasha Gusev received the 2015 ASHG Charles J. Epstein Trainee Award for his work, “Large-scale transcriptome-wide association study identifies new risk genes for obesity-related traits.” The award is given to the top 6 (out of over 3,000) abstracts submitted to the annual ASHG meeting.
After founding the Program in Molecular and Genetic Epidemiology (now the Program in Genetic Epidemiology and Statistical Genetics or PGSG) and overseeing its rapid growth (it has more than doubled in number of faculty, staff and trainees over the last 10 years) Professor David Hunter has stepped down as PGSG director to focus on his duties as Dean for Academic Affairs. Professor Peter Kraft is the new PGSG Director. Professor Kraft was deputy director of the PGSG from 2010 to 2014.
Congratulations to Alkes Price, who was recently promoted to Associate Professor of Statistical Genetics. Dr. Price has been at HSPH since 2008; his research focuses on the development of statistical methods for uncovering the genetic basis of human disease, and on the population genetics underlying these methods.
PGSG welcomes Wonil Chung and Yunhua Xiang, our two newest group members. Wonil is a Postdoctoral Fellow who recently received his Ph.D. from the University of North Carolina at Chapel Hill, while Yunhua is a Visiting Student from the Renmin University School of Statistics in Beijing. Both are working with Dr. Liming Liang.
PGSGers will have a strong showing at the major genetics conferences this Fall. Several students and researchers have been invited to showcase their work as poster and platform presentations at the annual American Society of Human Genetics Meeting, among others. Presentation details can be found here.
PGSG Deputy Director to Co-Direct AACR workshop
For the second year in a row, Peter Kraft will be Co-Director of an exciting workshop this summer in Boston, MA. The AACR’s Integrative Molecular Epidemiology Workshop is designed to accelerate the training of the next generation of cancer researchers. The workshop is primarily targeted toward molecular epidemiologists, but will also be a valuable experience for geneticists, statisticians, bioinformaticians, molecular biologists, physician scientists and others who have done basic course work in epidemiology. As Co-Director and member of the planning committee, Dr. Kraft has been very closely involved in organizing this event; Dr. Lorelei Mucci, Associate Professor of Epidemiology at HSPH, is also a workshop faculty member and member of the planning committee. The workshop was a great success when it was first held last year, and the organizers are working hard to put together another exciting learning experience for attendees.
The workshop is from August 11-15, 2014, in Boston. For more details visit the event website.
Epi in Space
An exciting new study led by NASA’s Human Research Program and the National Space Biomedical Research Institute will fund several investigations into the molecular, physiological and psychological effects of spaceflight in an effort to better understand the health impacts of human space exploration. Identical twins Scott and Mark Kelly, both veteran astronauts, will be the focus of this study. Scott Kelly will live aboard the International Space Station for one year while his twin brother, Mark Kelly, remains on Earth as a control. PI Immaculata De Vivo and lab manager Pati Soule are collaborating with researchers at Colorado State University to analyze the effect of spaceflight on telomeres. Telomeres are stretches of DNA found at the end of chromosomes; they shorten over time as cells divide and are associated with aging, cancer, and a higher risk of death. The project, “Differential effects on telomeres and telomerase in twin astronauts associated with spaceflight” will study astronaut Scott Kelly’s telomeres during his year in space and compare them to his twin. The researchers are excited to be a part of this first-of-its-kind investigation.
Symposium on Advances in Endometrial Cancer Epidemiology and Biology at HSPH
On March 17-18th Immaculata De Vivo hosted the Advances in Endometrial Cancer Epidemiology and Biology Symposium. The overall goal of the symposium was to identify priorities for future research that will have a strong impact on risk of and outcomes from endometrial cancer. Dr. De Vivo gave the opening and closing remarks, and also gave a presentation of her work on GWAS and XWAS results. Other notable speakers included Drs. David Hunter, Peter Kraft, and Jennifer Prescott, all members of PGSG. Many other researchers from multiple disciplines (epidemiologists, clinicians, and medical doctors) traveled from all over the country to attend the symposium. Karen Lu from MD Anderson Cancer Center, Sara Olson of Memorial Sloan-Kettering Cancer Center, and Wendy Setiawan from the University of Southern California were all co-organizers. The event was a huge success, and there is already talk of planning the next one!
PGSG is the new PMAGE
The Program in Molecular and Genetic Epidemiology has changed its name to the Program in Genetic Epidemiology and Statistical Genetics (PGSG). The new name reflects the Program’s expanded interest in statistical methods for genetic epidemiology, ranging from new methods to estimate the genetic contribution to disease risk (here, here, and here), integrate germline genetic variation, gene expression and methylation (here and here), and identify and interpret gene-environment interactions (here and here).
Program faculty, fellows and students continue to pursue research to understand the molecular mechanisms underlying complex diseases, using a wide range of biomarkers (here and here).
Liming Liang was lead author on a Genome Research paper describing new methods for analyzing expression quantitative trait loci (eQTLs) and a new freely available data base containing over 14,000 high-confidence eQTLs. This database can help define the function of disease-associated variants.
Rulla Tamimi published several papers on the links between obesity, mammographic density, and molecularly-defined breast cancer subtypes.
Hugo Aschard, a Research Associate in the PGSG, published a paper on non-parametric methods for genetic association in Genetic Epidemiology.
2013 PGSG Retreat
The 2013 PGSG Retreat took place on September 13th at the Wellesley College Club. Director David Hunter and Deputy Director Peter Kraft led a day of scientific presentations, lively discussion, and socializing. The presentations included a wide range of topics, from cancer to populations genetics, telomeres, and sequencing. With the PGSG group continuing to grow in recent years, the retreat is always a welcome opportunity to get to know new members and discuss potential new collaborations.
September 2013: Doctoral student Chia-yen Chen successfully defended his thesis on”Genetic prediction using genome-wide single nucleotide polymorphisms.” He will soon begin a postdoctoral fellowship at Massachusetts General Hospital with Jordan Smoller and Benjamin Neale. Congratulations Dr. Chen!
Dr. Jiali Han accepted an exciting new opportunity- effective September 1st, 2013, he is Professor and Department Chair of Epidemiology at the Richard M. Fairbanks School of Public Health, Efroymson Professor of Oncology, Simon Cancer Center, at Indiana University at Indianapolis. Dr. Han will also remain affiliated with HSPH as an adjunct professor in the Department of Epidemiology.
August 2013: Congratulations to Postdoctoral Fellow Xuefeng (Peter) Wang, who in August 2013 started a new position as a tenure-track assistant professor in the Program in Public Health and the Department of Preventive Medicine at Stony Brook University School of Medicine. During his time at HSPH, Xuefeng was jointly supervised by Dr. Liming Liang in the Department of Epidemiology and Dr. Xihong Lin in the Biostatistics Department. We wish him the best of luck!
Postdoc Chaolong Wang was selected as a semifinalist for the 2013 Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research for the 63rd Annual Meeting of the American Society of Human Genetics, which was held in Boston from October 22-26th, 2013. His abstract, “Tracing individual ancestry in a principal components space,” will be evaluated further for the finalist. Chaolong is mentored by Drs. Liming Liang and Xihong Lin.
Fall 2013: The De Vivo Lab has continued to grow in recent months, adding two new postdoctoral fellows and new summer researchers. The laboratory primarily focuses on the discovery and characterization of genetic biological markers to assess disease susceptibility in human populations. Biological markers of interest include single nucleotide polymorphisms (SNPs), telomere length, and gene copy number variations (CNVs). In addition the lab also collaborates in the characterization of potential cancer therapeutic agents such as GRN163L which attacks Telomerase, and Dichloroacetate, which attacks aerobic glycolysis. Welcome to all the new members!
Congratulations to all the 2013 graduates, especially Linda Hiraki and Maxine Chen! Dr. Hiraki completed her Ph.D. and is moving on to a postdoctoral position in her native Canada. Maxine received her Master’s degree, and will remain at HSPH as a Doctoral student this Fall.
Mentoring Future Epidemiologists
Each year the Department of Epidemiology runs a 4 week Summer Program for students from underrepresented backgrounds. The Summer Program in Epidemiology integrates mathematics and quantitative methods to provide students with an understanding of the skills and processes necessary to pursue a career in public health. This year Alkes Price, Assistant Professor of Statistical Genetics, is mentoring three students in the program. Dr. Price’s research focuses on the development of statistical methods for uncovering the genetic basis of human disease, and on the population genetics underlying these methods. In addition to coursework and lectures, his students are collaborating on a research project entitled, “Consistency across Ancestries of Genetic Associations to Type 2 Diabetes.” The project and coursework provide students an introduction to epidemiology and biostatistics, and give them the opportunity to learn about the many interdisciplinary approaches in public health from HSPH professors, students and researchers.
Peter Kraft and his colleague Cecile Janssens, Professor of Epidemiology at Emory University Rollins School of Public Health, have a paper published (October 2012) in PLoS Medicine about the limitations of “direct to consumer” research, such as 23andMe and the Personal Genome Project. These limitations mean that the results and conclusions of research using these methods need to be interpreted with caution. Other ethical concerns, such as disclosure of commercial development of research results and the sale of participants’ data to third parties, need to be considered and publicly debated.
The paper is available online here.
Postdoc Hugo Aschard and PMAGE Deputy Director Peter Kraft are featured on the Boston Globe website for their new paper, “Inclusion of Gene-Gene and Gene-Environment Interactions Unlikely to Dramatically Improve Risk Prediction for Complex Diseases” (AJHG May 2012). They were also interviewed for a press release on the main HSPH website about this important work. The full press release is available here.
Alkes Price and Gaurav Bhatia were interviewed for an article on the main HSPH website regarding their new paper, “Genome-wide comparison of African-Ancestry Populations from CARe and Other Cohorts Reveals Signals of Natural Selection” (AJHG Sep 2011). Click here to read the full article.
High-percent mammographic density is one of the strongest risk factors for breast cancer. In a January 2011 issue of Nature Genetics, PMAGE member Sara Lindstrom and colleagues reported a meta-analysis of five genome-wide association studies for percent mammographic density. They identified an associated locus in ZNF365, which has also been associated with susceptibility to breast cancer. This study might provide insights into the previously unexplained link between genetic variation in ZNF365 and breast cancer. PMAGE members Aditi Hazra, David Hunter, and Peter Kraft, as well as HSPH member Rulla Tamimi, were also significant contributors to this study.
Nature Genetics Online http://www.nature.com/ng/journal/v43/n3/full/ng.760.html
April 11, 2013 — In the largest-ever study of its kind, an international collaboration of hundreds of scientists has uncovered 74 new genetic markers linked to three common hormonal cancers—breast, prostate, and ovarian—thus setting the stage for new treatments, targeted screening, and a greater understanding of how these diseases develop.
Congratulations to the several PMAGE students, postdocs, and professors who have been selected to give talks and poster presentations at this year’s ASHG conference in Montreal, Canada. The conference is from October 11-14th, 2011. Special congrats to Gaurav Bhatia and Noah Zaitlen, who were both selected for a 2011 ASHG Trainee Research Semifinalist Award. To see details about PMAGE members’ presentations, please click here.
PGSG Deputy Director to Co-Direct new AACR workshop this Summer
Peter Kraft has been chosen to be Co-Director of an exciting new workshop this summer in Boston, MA. The AACR’s Integrative Molecular Epidemiology Workshop is designed to accelerate the training of the next generation of cancer researchers. The workshop is primarily targeted toward molecular epidemiologists, but will also be a valuable experience for geneticists, statisticians, bioinformaticians, molecular biologists, physician scientists and others who have done basic course work in epidemiology. Throughout the course of this workshop there will be both formal lectures and “laboratories” to build upon the lecture information. Participants will work collaboratively in small groups throughout the duration of the workshop. As Co-Director and member of the planning committee, Dr. Kraft has been very closely involved in organizing this event; Dr. Lorelei Mucci, Associate Professor of Epidemiology at HSPH, is also a workshop faculty member and member of the planning committee.
The workshop is from July 15-20, 2013, at the Seaport Hotel in Boston; applications were accepted through March 11th. For more information on this event visit the AACR website.
Mingfeng Zhang, who works with Dr. Jiali Han, has been selected to receive a Molecular Epidemiology Working Group of the American Association for Cancer Research (AACR) (MEG) Scholar-In-Training Award for the AACR 102nd Annual Meeting 2011, in Orlando, FL, USA, April 2-6, 2011. The MEG supports only three awards for the most meritorious proffered papers in molecular epidemiology! The title of her abstract is “Integrating Pathway Analysis amd Genetics of Gene Expression for Genome-wide Association Study of Basal Cell Carcinoma”.
Congratulations to Fengju Song and Mingfeng Zhang, who have been selected for press releases from the 10th AACR International Conference on Frontiers in Cancer Prevention Research, 2011. Both work with Dr. Jiali Han.
Coffee Consumption Associated With Decreased Risk for Basal Cell Carcinoma
Dr. Han and his research group have had their work on tanning beds and skin cancer highlighted in several recent news articles:
Journal of Clinical Oncology Editorial Commentary: Public Health and the Tanning Bed Controversy
Congratulations to Dr. Marina Kvaskoff, who received the Marie Curie Fellowship from the European Union’s Research Executive Agency in December 2011. Dr. Kvaskoff will use her fellowship to work on the link between melanoma and endometriosis with Drs. Stacey Missmer and Jiali Han.
Two PMAGE members received awards at the 2011 PQG Conference. Doctoral student Zhonghua Liu was selected for the 2011 PQG Student/Postdoc Travel Award, for his talk “Genome-wide association study on the variation of quantitative trait may help identify important genetic variants for complex diseases: an example of CHD risk in T2D patients.”
Postdoctoral Fellow Noah Zaitlen received the 2011 PQG Stellar Abstract Award.
Postdoctoral Fellow Bjarni Vilhjalmsson received a DFF-Individual postdoctoral grant to support his research.
Alkes Price was awarded R01 HG006399, “Methods for Genome-wide Association Studies in Admixed Populations.” The goal of this project is to develop improved statistical methods for disease mapping in populations of mixed ancestry, fully accounting for chromosomal segments of distinct continental ancestry in these populations. Collaborators include David Reich (HMS), Nick Patterson (Broad Institute), and Simon Myers (University of Oxford).
Liming Liang is a co-investigator on RC4 MH092707, “Using GWAS Data for Enhanced Mendelian Randomization Studies.” This proposal capitalizes on genome-wide association data to improve Mendelian Randomization techniques, which have been proposed to draw unbiased causal inferences from observational data.
Peter Kraft was awarded U01HG005922-01 “Sequencing regions associated with breast cancer risk in European and African Americans.” This project will sequence the regions spanning 10-15 common breast-cancer risk markers in 1,500 European-ancestry cases and 2,250 matched controls, as well as 500 African-American cases and 1000 matched controls. These data will provide substantive insight into the genetics of breast cancer, as well as guidance on the best design and analytic strategies for future sequencing studies. Liming Liang from PMAGE will provide key methodological support. Other collaborators include Xihong Lin and Alkes Price from HSPH; Shamil Sunyaev from HMS; and Chris Haiman, Dan Stram and Gary Chen from the University of Southern California.
David Hunter and Peter Kraft were among the Principal Investigators awarded U19CA148065-02, “Discovery, Biology and Risk of Inherited Variants in Breast Cancer.” This is a multi-project, multi -center project supported by the National Cancer Institute’s Transdisciplinary Cancer Genomics Initiative (http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-09-002.html). Dr. Hunter is the overall coordinating PI. Dr. Kraft is the coordinating PI for Project 3, which aims to understand the interplay between breast-cancer risk markers and modifiable risk factors and explore the utility of these markers for risk prediction and cancer prevention. The other projects will conduct a meta-analysis of existing breast-cancer genome-wide association studies to identify new markers (Doug Easton, co-ordinating PI) and study the biological mechanisms behind these markers (John Quackenbush, co-ordinating PI) . Collaborators include PMAGE member Aditi Hazra; Rulla Tamimi from HSPH; and Matt Freedman from HMS.
BPC3 Meeting at HSPH
PMAGE Director David Hunter and Deputy Director Peter Kraft are hosting the Breast and Prostate Cancer Cohort Consortium (BPC3) annual meeting at HSPH in October. The BPC3 was initiated in 2003 and funded for four years, with the aim to bring together large prospective cohort studies with more than 500 cases of breast cancer available for analysis. It includes nested case-control studies of breast and prostate cancer from eleven cohorts, and along with the Women’s Health Initiative (WHI) forms a key component of the breast cancer epidemiology project of the NCI post-GWAS initiative. In 2003, the BPC3 conducted one of the first large-scale, pathway-based candidate gene studies: a comprehensive study of the relationship between common genetic variation in steroid hormone and insulin-like growth factor pathways and risk of these two cancers. The BPC3 was funded in 2007 to conduct genome-wide association studies of aggressive prostate cancer and estrogen-receptor negative breast cancer. This work has led to two published papers identifying novel variants associated with prostate and breast cancer. These GWAS are also contributing to other collaborative meta-analyses, such as NCI Post-GWAS projects for breast and prostate cancer and the Collaborative Oncological Gene-environment Study.
2010 ASHG Talks
Alkes Price. Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals. Talk #191, Fri Nov 5, 9:00am-9:15am, Ballroom B, Level 3. In Session #43, “Genetic analysis of gene expression”.
Bogdan Pasaniuc. Enhanced disease scoring, imputation and fine-mapping for GWAS in admixed populations: assessment of increased power using African Americans from CARe. Talk #222, Fri Nov 5, 9:15-9:30am, Room 207, Level 2. In Session #46, “Genome-wide association studies and imputation”.
Noah Zaitlen. Conditioning on known associations improves the power of association studies. Talk #269, Fri Nov 5, 2:00-2:15pm, Ballroom B, Level 3. In Session #51, “Polygenic traits: GWAS methods and results”.
Alkes Price. Chromosomal segments in admixed individuals and inference of local ancestry. In “Complex disease genetics research in admixed populations”, Concurrent Invited Sessions I, Wed Nov 3, 8:00-10:00am, Ballroom A, Level 3.
Publications, publications everywhere
Manuscripts co-authored by PMAGErs David Hunter, Peter Kraft and Aditi Hazra have been freshly published or are about to appear in upcoming editions of top scientific journals. Scroll down to our Publications section for details and links to available articles!
June has proven a busy month for Alkes Price, PhD, who has seen not one, but two papers published in PLoS Genetics. Scroll down to our Publications section for details and links to the full text of both articles!
Better get there early if you want a seat…
A standing-room only crowd of over 100 attended a session, organized and chaired by Deputy Director Peter Kraft, on “building and evaluating genetic risk prediction models” at the Joint Statistial Meetings held from 2-5 August in Washington, DC. Mitch Gail from the National Cancer Instutute and Nancy Cook from Harvard Medical School and HSPH presented papers on alternative methods for measuring the clinical utility of risk prediction models. Tianxi Cai from HSPH spoke on flexible, multi-marker “pathway” tests that can detect genetic signatures associated with complex traits, and Dan Schaid from the Mayo clinic was the discussant.
Three Giant Steps for PMAGE-kind
David Hunter, MBBS, ScD, will assume the position of Dean for Academic Affairs at the Harvard School of Public Health on August 1st. Dr. Hunter began his career at HSPH in 1986 and has served as Director of the Program in Molecular and Genetic Epidemiolgy (PMAGE) since 2004.
Peter Kraft, PhD, will assume the position of Deputy Director of the Program in Molecular and Genetic Epidemiology at the Harvard School of Public Health on August 1st. Dr. Kraft first came to HSPH in 2003 and was instrumental in the development and implementation of PMAGE in 2004. In addition, he will also become Co-Director of the Program in Quantitative Genomics (PQG) on 1st August.
Immaculata De Vivo, PhD, has been named Director of the DF/HCC High-Throughput Polymorphism Detection Core. She will officially succeed David Hunter as Core Director on October 1st. Dr. De Vivo began her Harvard career in 1998 and has been a key Member of the Program since its inception.
Commencement 2009: Chunyan He
It is with mixed emotions that we celebrate Chunyan He’s graduation from the School of Public Health on June 4th. Chunyan has been a post-doctoral student in the Program for the past 5 years and has accepted a faculty position in the Department of Public Health at the University of Indiana. We thank her for 5 years of hard work and congratulate her on her swift success. We wish her the best of luck in her future endeavors, and most of all — we will miss her!
PRESS RELEASES, PUBLICATIONS AND INTERVIEWS
New genetic determinants of plasma B12, B6 and homocysteine discovered
In prospective studies lower plasma folate, vitamin B6 or B12, and increased plasma homocysteine levels are associated with colorectal cancer, pancreatic cancer, prostate cancer and breast cancer particularly among those who consume moderate to high levels of alcohol, which interferes with folate metabolism. In an upcoming issue of Human Molecular Geneteics, PMAGE member Aditi Hazra and colleagues report a genome-wide association study for plasma homocysteine, plasma folate, vitamin B12 and vitamin B6. Novel genome-wide significant associations include SNPs in MUT and plasma vitamin B12, ALPL and plasma vitamin B6, and GPR51 and plasma homocysteine. These data will elucidate which population subgroups may benefit most from additional B-vitamin intake due to genetic variation in B-vitamin metabolism or absorption.
Human Molecular Genetics, http://hmg.oxfordjournals.org/
PMAGE members Peter Kraft and David Hunter are co-authors on a paper linking genetic variation at the ABO blood group locus to risk of pancreatic cancer1. This paper was highlighted as an “Editor’s Pick” in the 28 August 2009 issue of Science magazine. Although rare, pancreatic cancer is still very difficult to treat and sadly quite lethal–it is the 3rd
leading cause of cancer mortality in the United States2. ABO blood groups are associated with immune surveillance and inflammatory response; this intriguing finding may lead to novel insights into the biology of pancreatic cancers and potential treatments.
Another senior author, Harvard Medical School Associate Professor Charles Fuchs, played a key role in organizing the PanScan Project in the fall of 2006. PanScan is funded by NCI’s Epidemiology and Genetics Research Program (EGRP) and is a collaboration of investigators at 13 institutions, including the National Cancer Institute, to investigate the genetics of pancreatic cancer.
1 Amundadottir L, Kraft P, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986-90. Epub 2009 Aug 2
2 American Cancer Society 2009, http://www.cancer.org/docroot/home/index.asp
Nature and Nature Genetics online: http://www.nature.com/
Faculty member Alkes Price demonstrates the utility and precision of HAPMIX software in the inference of local ancestry and its recent application to African-American and Mozabite haplotypes.
PLoS Genet. 2009 Jun;5(6):e1000505. Epub 2009 Jun 5. PMCID: PMC2684636 http://www.plosgenetics.org/
Sensitive detection of chromosomal segments of distinct ancestry in admixed populations
PMAGE Faculty Alkes Price shows how the regional geographic ancestry of individuals from Iceland was determined using dense genotype data and that allele frequency differences between regions of Iceland are due to genetic drift since the settling of Iceland, rather than ancestral populations.
PLoS Genet. 2009 Jun;5(6):e1000519. Epub 2009 Jun 19. PMCID: PMC2689842 http://www.plosgenetics.org/
Wahrsager Im Labor (Prophets in the Laboratory)
Deputy Director Peter Kraft was quoted in a feature in the 25 May edition of German magazine Der Spiegel. The article focused on the effectiveness of genome analysis, and the manner in which data are presented in scientific publications. Also quoted was David Altshuler of the Broad Institute of Harvard and MIT.
25 May 2009, Der Spiegel Nr. 22/25.5.09 p. 128-30 http://www.spiegel.de/
GENOMICS: Personal Risk Prediction: Not There Yet
PMAGE Director David Hunter and Faculty member Peter Kraft among the researchers who discuss the effectiveness of increasingly popular personal genome scans and individual risk tests.
17 April 2009, FOCUS Online
Genes show Limited Value in Predicting Diseases
Director David Hunter and Faculty member Peter Kraft were quoted in an article on the inefficacy of current personal genomic testing methodologies.
16 April 2009, The New York Times p. A1 www.nytimes.com/
Newly Identified Genetic Variants Found to Increase Breast Cancer Risk
Two common genetic variants that increase the risk of breast cancer in women of European ancestry have been identified in a large collaborative study of genetic markers. The manuscript has been published in the advance online section of Nature Genetics.
29 March 2009, HSPH Press Release
PMAGE Retreat 2009
On 9 March 2009, the Program held a day-long retreat at the Harvard Club on Commonwealth Ave. The Retreat gave PMAGE faculty, staff and post-doctoral students the opportunity to present data, increase their understanding of each others’ roles within the Program, and engage in dialogue about progress and goals for the future.
DNA Test for Breast Cancer Risk Draws Criticism
deCODE Genetics, an Icelandic company, released the first-ever breast cancer risk test designed to cover common forms of the disease amid much controversy.
17 October 2008, SCIENCE Vol. 322, published by AAAS. www.sciencemag.org
Nutrigenomics study reveals surprising genetic predictor of blood levels of vitamin known to be deficient in some elderly people.
7 September 2008, HSPH Press Release
Q&A with Co-author David Hunter of Harvard School of Public Health on Genome Scans and Pitfalls of Personal Profiling.
10 February, 2008 HSPH Press Release
Nicotine, Smoking and Genetics
Stephen Chanock, David Hunter and Kari Stefansson discuss how one’s genes can affect one’s addiction to nicotine and increased cancer risk from smoking.
2 April, 2008 Nature; Nature Genetics
First-ever release of results from a whole genome association study to the scientific community
The National Cancer Institute has released data on 310,000 SNPs in 1100 cases of prostate cancer and 1100 controls from the PLCO study. Primary results from the study are freely available on the web at: http://cgems.cancer.gov. This data release is part of the NCI CGEMS study co-directed by David Hunter, and is the first of its kind.
18 October, 2006 NCI/CGEMS
Program scientists confirm new gene for type II diabetes
Cuilin Zhang, working with Associate Professor Frank Hu of the Department of Nutrition, has confirmed that variants in the TCF7L2 gene are associated with risk of type II diabetes in women and men.
Inherited genetic variation associated with plasma triglyceride and HDL cholesterol levels
Lu Qi, working with Associate Professor Frank Hu of the Department of Nutrition, has shown that variants at the apolipoprotein A1/C3/A4/A5 locus predict levels of plasma lipids.
Information on genes improves risk prediction for skin cancer risk
Jiali Han shows that incorporating information on variants of the MC1R gene modestly improved the ability to predict risk of skin cancer, compared with the traditional risk factors such as hair color and skin response to sun exposure. This is one of the first demonstrations that incorporating information on common variants in genes can improve risk prediction models.
Program scientists identify genetic variant as new risk factor for colorectal cancer
Working with MIT scientists, Greg Tranah identified a variant in the MGMT DNA repair gene as associated with reduced risk of colorectal cancer.
Program scientist helps identify new risk factor for diabetes and heart disease
Immaculata De Vivo, Associate Professor of Epidemiology, collaborated with Eric Rimm of the Department of Epidemiology and investigators in the Department of Molecular Metabolism to help identify a new gene variant associated with risk of diabetes and heart disease.
Effect of genotyping misclassification on genetic epidemiology studies documented
PMAGE Statistician and Associate Professor of Epidemiology and Biostatistics Peter Kraft, working with postdoctoral fellow Usha Govindarajulu, shows that genotyping error can have a greater effect than previously appreciated on the results from genetic epidemiology studies.
New locus identified for obesity
In collaboration with scientists at Boston University, Christoph Lange, Nan Laird from the Department of Biostatistics, PMAGE Director David Hunter and others participated in the identification of a potential new genetic risk factor for obesity.
Novel Coalescence-guided Hierarchical Bayesian (CHB) method for haplotype inference developed
Tianhua Niu, Assistant Professor of Epidemiology, working with Professor Jun S. Liu in the Department of Statistics and postdoctoral fellow Yu Zhang, developed a novel and efficient algorithm for haplotype inference. Called “CHB”, this has merits in performance compared with other popular software programs, such as HAPLOTYPER and PHASE.
Professor David Hunter to Lead New Program in Molecular and Genetic Epidemiology
20 February, 2004 Harvard Public Health NOW