title: Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.
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.
authors: Harvard- Massachusetts Institute of Technology (MIT) Division of Health, Science and Technology, Cambridge, USA. gbhatia@mit.edu
authors: Gaurav
authors: G
authors: Bhatia
authors: Nick
authors: N
authors: Patterson
authors: Bogdan
authors: B
authors: Pasaniuc
authors: Noah
authors: N
authors: Zaitlen
authors: Giulio
authors: G
authors: Genovese
authors: Samuela
authors: S
authors: Pollack
authors: Swapan
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authors: Mallick
authors: Simon
authors: S
authors: Myers
authors: Arti
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authors: Tandon
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authors: Spencer
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authors: CD
authors: Palmer
authors: Adebowale A
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authors: Adeyemo
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authors: EL
authors: Akylbekova
authors: L Adrienne
authors: LA
authors: Cupples
authors: Jasmin
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authors: Divers
authors: Myriam
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authors: Fornage
authors: W H Linda
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authors: Kao
authors: Leslie
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authors: Lange
authors: Mingyao
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authors: Li
authors: Solomon
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authors: Musani
authors: Josyf C
authors: JC
authors: Mychaleckyj
authors: Adesola
authors: A
authors: Ogunniyi
authors: George
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authors: Papanicolaou
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authors: CN
authors: Rotimi
authors: Jerome I
authors: JI
authors: Rotter
authors: Ingo
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authors: Ruczinski
authors: Babatunde
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authors: Salako
authors: David S
authors: DS
authors: Siscovick
authors: Bamidele O
authors: BO
authors: Tayo
authors: Qiong
authors: Q
authors: Yang
authors: Steve
authors: S
authors: McCarroll
authors: Pardis
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authors: Sabeti
authors: Guillaume
authors: G
authors: Lettre
authors: Phil
authors: P
authors: De Jager
authors: Joel
authors: J
authors: Hirschhorn
authors: Xiaofeng
authors: X
authors: Zhu
authors: Richard
authors: R
authors: Cooper
authors: David
authors: D
authors: Reich
authors: James G
authors: JG
authors: Wilson
authors: Alkes L
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authors: Price
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics; D044383:Black People / Q000235:genetics*; D018955:CD36 Antigens / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D005714:Gambia; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics; D009549:Nigeria; D012641:Selection, Genetic; D014481:United States
chemical_list: D000951:Antigens, Neoplasm; D018955:CD36 Antigens; D058851:GPI-Linked Proteins; D006680:HLA Antigens; D009363:Neoplasm Proteins; C110843:PSCA protein, human