Steven McCarroll, Ph.D.
Dorothy and Milton Flier Associate Professor of Biomedical Science and Genetics
Department of Genetics, Harvard Medical School
Director of Genetics, Broad Institute’s Stanley Center for Psychiatric Research
Complex forms of genome variation in human disease
Complex and multi-allelic forms of human genome variation exist in many different common structural forms in different individuals. These forms of genome variation have been largely invisible to genome-wide association studies based on genome-wide SNP genotyping and exome sequencing. I will describe our work to make these forms of variation visible to whole genome sequencing and imputation. Through this work, we have discovered that complex, multi-allelic forms of variation are among the human genome’s largest influences on risk of schizophrenia and cardiovascular disease. We have found that complex variation gives rise to natural allelic series in which the presence of many different risk levels (for different alleles), and the recurrence of specific alleles on different haplotype backgrounds, create new opportunities to find the functional alleles and their effects on biological systems.
