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PMID: 21907010 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

American journal of human genetics ·Vol. 89 ·No. 3 ·2011-09-09 ·Pages 368-81

Bhatia G, Patterson N, Pasaniuc B, Zaitlen N, Genovese G, Pollack S, Mallick S, Myers S, Tandon A, Spencer C, Palmer CD, Adeyemo AA, Akylbekova EL, Cupples LA, Divers J, Fornage M, Kao WH, Lange L, Li M, Musani S, Mychaleckyj JC, Ogunniyi A, Papanicolaou G, Rotimi CN, Rotter JI, Ruczinski I, Salako B, Siscovick DS, Tayo BO, Yang Q, McCarroll S, Sabeti P, Lettre G, De Jager P, Hirschhorn J, Zhu X, Cooper R, Reich D, Wilson JG, Price AL

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.

MeSH Terms
African Americans/genetics Antigens, Neoplasm/genetics Blacks/genetics CD36 Antigens/genetics GPI-Linked Proteins/genetics Gambia Gene Frequency Genetic Variation Genetics, Population Genome, Human/genetics Genotype HLA Antigens/genetics Humans Models, Genetic Neoplasm Proteins/genetics Nigeria Selection, Genetic United States
Chemicals
Antigens, Neoplasm CD36 Antigens GPI-Linked Proteins HLA Antigens Neoplasm Proteins PSCA protein, human
Authors & Affiliations
40 authors, click to expand affiliations / ORCID
Bhatia Gaurav
Harvard- Massachusetts Institute of Technology (MIT) Division of Health, Science and Technology, Cambridge, USA. [email protected]
Patterson Nick
Pasaniuc Bogdan
Zaitlen Noah
Genovese Giulio
Pollack Samuela
Mallick Swapan
Myers Simon
Tandon Arti
Spencer Chris
Palmer Cameron D
Adeyemo Adebowale A
Akylbekova Ermeg L
Cupples L Adrienne
Divers Jasmin
Fornage Myriam
Kao W H Linda
Lange Leslie
Li Mingyao
Musani Solomon
Mychaleckyj Josyf C
Ogunniyi Adesola
Papanicolaou George
Rotimi Charles N
Rotter Jerome I
Ruczinski Ingo
Salako Babatunde
Siscovick David S
Tayo Bamidele O
Yang Qiong
McCarroll Steve
Sabeti Pardis
Lettre Guillaume
De Jager Phil
Hirschhorn Joel
Zhu Xiaofeng
Cooper Richard
Reich David
Wilson James G
Price Alkes L
References (60)
60 references, click to expand
  1. Population-genetic properties of differentiated human copy-number polymorphisms.
    Am J Hum Genet. 2011 Mar 11;88(3):317-32 PMID: 21397061
  2. Interrogating a high-density SNP map for signatures of natural selection.
    Genome Res. 2002 Dec;12(12):1805-14 PMID: 12466284
  3. Genetics in geographically structured populations: defining, estimating and interpreting F(ST).
    Nat Rev Genet. 2009 Sep;10(9):639-50 PMID: 19687804
  4. Association of the OCA2 polymorphism His615Arg with melanin content in east Asian populations: further evidence of convergent evolution of skin pigmentation.
    PLoS Genet. 2010 Mar 05;6(3):e1000867 PMID: 20221248
  5. A map of recent positive selection in the human genome.
    PLoS Biol. 2006 Mar;4(3):e72 PMID: 16494531
  6. Spatial patterns of variation due to natural selection in humans.
    Nat Rev Genet. 2009 Nov;10(11):745-55 PMID: 19823195
  7. Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.
    Tissue Antigens. 2004 Apr;63(4):293-325 PMID: 15009803
  8. Genome-wide and fine-resolution association analysis of malaria in West Africa.
    Nat Genet. 2009 Jun;41(6):657-65 PMID: 19465909
  9. A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.
    Nat Genet. 2006 Oct;38(10):1166-72 PMID: 16998491
  10. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.
    PLoS Genet. 2011 Feb 10;7(2):e1001300 PMID: 21347282
  11. Adaptations to climate in candidate genes for common metabolic disorders.
    PLoS Genet. 2008 Feb;4(2):e32 PMID: 18282109
  12. Genetic signatures of strong recent positive selection at the lactase gene.
    Am J Hum Genet. 2004 Jun;74(6):1111-20 PMID: 15114531
  13. Association of trypanolytic ApoL1 variants with kidney disease in African Americans.
    Science. 2010 Aug 13;329(5993):841-5 PMID: 20647424
  14. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.
    Nat Genet. 2008 Jun;40(6):730-40 PMID: 18488030
  15. Sequencing of 50 human exomes reveals adaptation to high altitude.
    Science. 2010 Jul 2;329(5987):75-8 PMID: 20595611
  16. The genetic structure and history of Africans and African Americans.
    Science. 2009 May 22;324(5930):1035-44 PMID: 19407144
  17. Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B.
    PLoS Pathog. 2007 Sep 21;3(9):1240-9 PMID: 17892322
  18. Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation.
    Am J Hum Genet. 2002 Jan;70(1):207-23 PMID: 11741197
  19. Genomic dissection of population substructure of Han Chinese and its implication in association studies.
    Am J Hum Genet. 2009 Dec;85(6):762-74 PMID: 19944404
  20. The impact of divergence time on the nature of population structure: an example from Iceland.
    PLoS Genet. 2009 Jun;5(6):e1000505 PMID: 19503599
  21. Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
    Am J Hum Genet. 2007 Aug;81(2):234-42 PMID: 17668374
  22. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.
    Nat Genet. 2010 Sep;42(9):739-741 PMID: 20694014
  23. The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs.
    Hum Genomics. 2004 May;1(4):274-86 PMID: 15588487
  24. The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.
    Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R176-81 PMID: 16987881
  25. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.
    Nat Genet. 2009 Sep;41(9):991-5 PMID: 19648920
  26. Genetic evidence for high-altitude adaptation in Tibet.
    Science. 2010 Jul 2;329(5987):72-5 PMID: 20466884
  27. Integrating common and rare genetic variation in diverse human populations.
    Nature. 2010 Sep 2;467(7311):52-8 PMID: 20811451
  28. Methods for high-density admixture mapping of disease genes.
    Am J Hum Genet. 2004 May;74(5):979-1000 PMID: 15088269
  29. A genome-wide approach to identify genetic loci with a signature of natural selection in the Irish population.
    Genome Biol. 2006;7(8):R74 PMID: 16904005
  30. A human genome diversity cell line panel.
    Science. 2002 Apr 12;296(5566):261-2 PMID: 11954565
  31. Evidence for balancing selection at HLA.
    Genetics. 1983 Jul;104(3):449-56 PMID: 6884768
  32. Genome-wide detection and characterization of positive selection in human populations.
    Nature. 2007 Oct 18;449(7164):913-8 PMID: 17943131
  33. Constructing genomic maps of positive selection in humans: where do we go from here?
    Genome Res. 2009 May;19(5):711-22 PMID: 19411596
  34. A haplotype map of the human genome.
    Nature. 2005 Oct 27;437(7063):1299-320 PMID: 16255080
  35. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes.
    Genet Epidemiol. 2010 Dec;34(8):816-34 PMID: 21058334
  36. Positive natural selection in the human lineage.
    Science. 2006 Jun 16;312(5780):1614-20 PMID: 16778047
  37. Classic selective sweeps were rare in recent human evolution.
    Science. 2011 Feb 18;331(6019):920-4 PMID: 21330547
  38. Detecting recent positive selection in the human genome from haplotype structure.
    Nature. 2002 Oct 24;419(6909):832-7 PMID: 12397357
  39. Widespread genomic signatures of natural selection in hominid evolution.
    PLoS Genet. 2009 May;5(5):e1000471 PMID: 19424416
  40. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.
    PLoS Genet. 2010 Sep 09;6(9):e1001116 PMID: 20838600
  41. Localizing recent adaptive evolution in the human genome.
    PLoS Genet. 2007 Jun;3(6):e90 PMID: 17542651
  42. Sensitive detection of chromosomal segments of distinct ancestry in admixed populations.
    PLoS Genet. 2009 Jun;5(6):e1000519 PMID: 19543370
  43. A whole-genome association study of major determinants for host control of HIV-1.
    Science. 2007 Aug 17;317(5840):944-7 PMID: 17641165
  44. Evolutionary relationships of human populations from an analysis of nuclear DNA polymorphisms.
    Nature. 1986 Feb 6-12;319(6053):491-3 PMID: 3003580
  45. Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations.
    Am J Hum Genet. 2011 Jun 10;88(6):741-754 PMID: 21664997
  46. Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus.
    Am J Hum Genet. 2000 May;66(5):1669-79 PMID: 10762551
  47. Population structure and eigenanalysis.
    PLoS Genet. 2006 Dec;2(12):e190 PMID: 17194218
  48. Natural selection has driven population differentiation in modern humans.
    Nat Genet. 2008 Mar;40(3):340-5 PMID: 18246066
  49. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  50. A second generation human haplotype map of over 3.1 million SNPs.
    Nature. 2007 Oct 18;449(7164):851-61 PMID: 17943122
  51. Phylogenetic analysis. Models and estimation procedures.
    Am J Hum Genet. 1967 May;19(3 Pt 1):233-57 PMID: 6026583
  52. Measures of human population structure show heterogeneity among genomic regions.
    Genome Res. 2005 Nov;15(11):1468-76 PMID: 16251456
  53. Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.
    Hum Mol Genet. 2009 Jul 15;18(14):2683-92 PMID: 19403559
  54. Population structure, differential bias and genomic control in a large-scale, case-control association study.
    Nat Genet. 2005 Nov;37(11):1243-6 PMID: 16228001
  55. How malaria has affected the human genome and what human genetics can teach us about malaria.
    Am J Hum Genet. 2005 Aug;77(2):171-92 PMID: 16001361
  56. Genetic evidence for the convergent evolution of light skin in Europeans and East Asians.
    Mol Biol Evol. 2007 Mar;24(3):710-22 PMID: 17182896
  57. Common variants in the trichohyalin gene are associated with straight hair in Europeans.
    Am J Hum Genet. 2009 Nov;85(5):750-5 PMID: 19896111
  58. Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.
    PLoS Genet. 2011 Apr;7(4):e1001371 PMID: 21541012
  59. Population genetics of malaria resistance in humans.
    Heredity (Edinb). 2011 Oct;107(4):283-304 PMID: 21427751
  60. Recent and ongoing selection in the human genome.
    Nat Rev Genet. 2007 Nov;8(11):857-68 PMID: 17943193
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2011.07.025
Email
[email protected]
Published
2011-09-09
Pages
368-81
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC3169818
Subset
IM
Grants
NHGRI NIH HHS · R01 HG005224 · United States
NIEHS NIH HHS · 5T32ES007142-27 · United States
NHGRI NIH HHS · R01 HG006399 · United States
NHGRI NIH HHS · R03 HG006170 · United States
NHGRI NIH HHS · T32 HG002295 · United States
Wellcome Trust · 090532 · United Kingdom
NHGRI NIH HHS · U01 HG004726-01 · United States
NHGRI NIH HHS · U01 HG004726 · United States
NIGMS NIH HHS · RC1 GM091332 · United States
NIEHS NIH HHS · T32 ES007142 · United States
External Links
PubMed source DOI: 10.1016/j.ajhg.2011.07.025 PMC Full Text View journal details
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