Authors

Gaurav Bhatia, Massachusetts Institute of Technology
Nick Patterson, Massachusetts Institute of Technology
Bogdan Pasaniuc, Massachusetts Institute of Technology
Noah Zaitlen, Massachusetts Institute of Technology
Giulio Genovese, Harvard Medical School
Samuela Pollack, Massachusetts Institute of Technology
Swapan Mallick, Massachusetts Institute of Technology
Simon Myers, University of Oxford
Arti Tandon, Massachusetts Institute of Technology
Chris Spencer, The Wellcome Centre for Human Genetics
Cameron D. Palmer, Massachusetts Institute of Technology
Adebowale A. Adeyemo, National Human Genome Research Institute (NHGRI)
Ermeg L. Akylbekova, Jackson State University
L. Adrienne Cupples, Boston University
Jasmin Divers, Wake Forest University School of Medicine
Myriam Fornage, University of Texas School of Public Health
W. H.Linda Kao, Johns Hopkins University
Leslie Lange, UNC School of Medicine
Mingyao Li, University of Pennsylvania
Solomon Musani, University of Mississippi Medical Center
Josyf C. Mychaleckyj, University of Virginia School of Medicine
Adesola Ogunniyi, University of Ibadan
George Papanicolaou, National Heart, Lung, and Blood Institute (NHLBI)
Charles N. Rotimi, National Human Genome Research Institute (NHGRI)
Jerome I. Rotter, Cedars-Sinai Medical Center
Ingo Ruczinski, Johns Hopkins University
Babatunde Salako, University of Ibadan
David S. Siscovick, University of Washington
Bamidele O. Tayo, Stritch School of Medicine
Qiong Yang, Boston University
Steve McCarroll, Massachusetts Institute of Technology
Pardis Sabeti, Harvard University
Guillaume Lettre, Institut de Cardiologie de Montreal

Document Type

Article

Publication Date

9-9-2011

Abstract

The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F ST < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10 -11) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers. © 2011 The American Society of Human Genetics.

Publication Source (Journal or Book title)

American Journal of Human Genetics

First Page

368

Last Page

381

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