David Altshuler Laboratory

Despite great progress in medical science, we have limited knowledge of the determinants of disease risk in vivo in the human population, and of targets for prevention and treatment. As family history is a strong and largely unexplained risk factor for human diseases, and given rapid development of methods for studying human genome variation, human genetics offers a promising approach to expand our knowledge of human diseases mechanisms.

Until recently, studies of human genetics were limited to family-based linkage studies, and to candidate gene association studies, neither of which have proven generally successful in studies of complex, common diseases. While linkage studies were genome-wide, and thus could discover novel information about disease mechanisms, association studies were previously limited to preconceived hypotheses about which genes might be responsible.

Our lab has worked to make possible systematic studies of common genetic variants for association to disease. We played leadership roles in the SNP Consortium and HapMap Projects, and in the development of affordable genome-wide genotyping technologies to enable whole-genome association studies in large clinical samples. We have developed statistical methods and standards to support robust and reproducible gene discovery from population-based association studies.

In the past year, whole genome association studies have uncovered novel and reproducible SNP associations for a wide variety of common diseases. We have contributed to gene discovery in type 2 diabetes, hyperlipidemia, prostate cancer, age-related macular degeneration, rheumatoid arthritis, and systemic lupus erythematosis. We are pursuing these new leads to gain insight into disease mechanisms, and to develop new targets for therapeutic intervention and disease prevention.

Publications Supplementary Data

Online supplementary data for some of the research papers published on these topics can be found here.