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.
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 Genetics and Complex Diseases 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