The Altshuler Lab uses human genetics to discover novel pathophysiological processes underlying risk of type 2 diabetes (T2D). Our first decade focused on making it possible to discover genes and variants underlying common, complex diseases: studies of human genetic variation, development of laboratory and analytical methods, and leadership in The SNP Consortium, International HapMap and 1000 Genomes Projects.  We have identified ≈70 loci contributing to risk of T2D, and hundreds contributing to myocardial infarction, glycemic traits, lipids and other diseases.  The laboratory now pursues two main approaches: (a) whole exome and genome sequencing to systematically characterize rare mutations in T2D, and (b) discovering the biological functions of the genes and mutations found, with a long-term goal of identifying and validating drug targets. 

1. 1000 Genomes Project Consortium “A map of human genome variation from population-scale sequencing”. Nature 2010 Oct 28;467(7319):1061-73. PMCID: PMC3042601  (*DA is Co-Chair of the Project and Member of the Writing Group for this manuscript)

2. Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI; DIAGRAM; MAGIC, Altshuler, D, Daley GQ (2011)  “The Lin28/let-7 axis regulates glucose metabolism” Cell 147:81-94 PMCID: PMC3353524

3. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ. “A framework for variation discovery and genotyping using next-generation DNA sequencing data”. Nature Genetics 2011 May;43(5):491-8. PMCID: PMC3083463

4. Voight BF, Peloso GM, Orho-Melander M…[116 authors]…Stefansson K, O’Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz SM, Altshuler D, Kathiresan S. “Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study”. Lancet. 2012 Aug 11;380(9841):572-80. Epub 2012 May 17. PMCID: PMC3419820

5. Flannick J, Beer NL, Bick AG, Agarwala V, Molnes J, Gupta N, Burtt NP, Florez JC, Meigs JB, Taylor H, Lyssenko V, Irgens H, Fox E, Burslem F, Johansson S, Brosnan MJ, Trimmer JK, Newton-Cheh C, Tuomi T, Molven A, Wilson JG, O’Donnell CJ, Kathiresan S, Hirschhorn JN, Njølstad PR, Rolph T, Seidman JG, Gabriel S, Cox DR, Seidman CE, Groop L, Altshuler D (2013) “Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes.”  Nature Genetics Nov;45(11):1380-5. doi: 10.1038/ng.2794. PMCID in process

6.Plenge RM, Scolnick EM, Altshuler D. “Validating therapeutic targets through human genetics.” Nature Reviews Drug Discovery. 2013 Aug;12(8):581-94.

7. Agarwala V, Flannick J, Sunyaev S; GoT2D Consortium, Altshuler D. “Evaluating empirical bounds on       complex disease genetic architecture.” Nat Genet. 2013 Dec;45(12):1418-27. PMCID in process
The SIGMA Type 2 Diabetes Consortium (2014) “Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico” Nature. 506(7486):97-101  (DA is Principal Investigator, senior and corresponding author). PMCID in process

8. Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup…[77 authors]…, Boehnke M, McCarthy MI, Njølstad PR, Pedersen O, Groop L, Cox DR, Stefansson K, Altshuler D. “Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.” Nature Genetics 2014 Mar 2. doi: 10.1038/ng.2915. PMCID in process