Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations?

English version České info

Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS.

Vyšlo v časopise: Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations?. PLoS Genet 7(1): e32767. doi:10.1371/journal.pgen.1001266
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001266

Souhrn

Zdroje

1. SaleMM

MychaleckyjJC

ChenW-M

2009 Planning and Executing a Genome Wide Association Study (GWAS).

Park-SargeQ-K

CurryTE

Molecular Endocrinology: Methods and Protocols New York Humana Press 403 418

2. DicksonSP

WangK

KrantzI

HakonarsonH

GoldsteinD

2010 Rare Variants Create Synthetic Genome-Wide Associations. PLoS Biology 8 e1000294

3. WangK

DicksonSP

StolleCA

KrantzID

GoldsteinDB

2010 Interpretation of Association Signals and Identification of Causal Variants from Genome-wide Association Studies. American Journal of Human Genetics 86 730 742

4. HindorffLA

SethupathyP

JunkinsHA

RamosEM

MehtaJP

2009 Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Science USA 106 9362 9367

5. HindorffLA

JunkinsHA

MehtaJP

ManolioTA

2010 A Catalog of Published Genome-Wide Association Studies. Available at: www.genome.gov/gwastudies. Accessed May 13, 2010.

6. AltshulerD

DalyMJ

LanderES

2008 Genetic Mapping in Human Disease. Science 322 881 888

7. PickrellJK

CoopG

NovembreJ

KudaravalliS

LiJZ

2009 Signals of recent positive selection in a worldwide sample of human populations. Genome Research 19 826 837

8. MylesS

DavisonD

BarrettJ

StonekingM

TimpsonN

2008 Worldwide population differentiation at disease-associated SNPs. BMC Medical Genomics 1 22

9. LohmuellerKE

MauneyMM

ReichD

BravermanJM

2006 Variants associated with common disease are not unusually differentiated in frequency across populations. American Journal of Human Genetics 78 130 136

10. AdeyemoA

RotimiC

2010 Genetic Variants Associated with Complex Human DiseasesShow Wide Variation across Multiple Populations. Public Health Genomics 13 72 79

11. MatteiJ

ParnellLD

LaiC-Q

Garcia-BailoB

AdiconisX

2009 Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto-Ricans and non-Hispanic whites. BMC Genetics 10 45

12. LiJZ

AbsherDM

TangH

SouthwickAM

CastoAM

2008 Worldwide human relationships inferred from genome-wide patterns of variation. Science 2008, 319 1100 1104

13. RosenbergNA

PritchardJK

WeberJL

CannHM

KiddKK

2002 Genetic structure of human populations. Science 298 2381 2385

14. CastoAM

LiJZ

AbsherD

MyersR

RamachandranS

2010 Characterization of X-linked SNP genotypic variation in globally-distributed human populations. Genome Biology 11 R10

15. VoightBF

KudaravalliS

WenX

PritchardJK

2006 A map of recent positive selection in the human genome. PLOS Biology 4 446 458

16. MeyreD

DelplanqueJ

ChèvreJC

LecoeurC

LobbensS

2009 Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nature Genetics 41 157 159

17. LevyD

EhretGB

RiceK

VerwoertGC

LaunetLJ

2009 Genome-wide association study of blood pressure and hypertension. Nature Genetics 41 677 687

18. LimouS

Le ClercS

CoulongesC

CarpentierW

DinaC

2009 Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes. Journal of Infectious Disease 199 419 426

19. LiuY

HelmsC

LiaoW

ZabaLC

DuanS

2008 A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genetics 4 e1000041

20. LandiMT

ChatterjeeN

YuK

GoldinLR

GoldsteinAM

2009 A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. American Journal of Human Genetics 85 679 691

21. YangJJ

ChengC

YangW

PeiD

CaoX

2009 Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. Journal of the American Medical Association 301 393 403

22. Newton-ChehC

JohnsonT

GatevaV

TobinMD

BochudM

2009 Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics 41 666 676

23. OkadaY

KamataniY

TakahashiA

MatsudaK

HosonoN

2010 A genome-wide association study in 19,633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. Human Molecular Genetics 19 2203 2312

24. KimJJ

LeeHI

ParkT

KimK

LeeJE

2010 Identification of 15 loci influencing height in a Korean population. American Journal of Human Genetics 55 27 31

25. ChoYS

GoMJ

KimYJ

HeoJY

OhJH

2009 A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nature Genetics 41 527 534

26. LeiSF

YangTL

TanLJ

ChenXD

GuoY

2009 Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci. Human Genetics 125 1 9

27. TsaiFJ

YangCF

ChenCC

ChuangLM

LuCH

2010 A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genetics 6 e1000847

28. TakeuchiF

SerizawaM

YamamotoK

FujisawaT

NakashimaE

2009 Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in a Japanese population. Diabetes 58 1690 1699

29. UnokiH

TakahashiA

KawaguchiT

HaraK

HorikoshiM

2008 SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature Genetics 40 1098 1102

30. YasudaK

MiyakeK

HorikawaY

HaraK

OsawaH

2008 Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nature Genetics 40 1092 1097

31. YangW

ShenN

YeDQ

LiuQ

ZhangY

2010 Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 association with systemic lupus erythematosus. PLoS Genetics 12 e1000841

32. HanJW

ZhengHF

CuiY

SunLD

YeDQ

2009 Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nature Genetics 41 1234 1237

33. FellayJ

GeD

ShiannaKV

ColomboS

LedergerberB

2009 Common genetic variation and the control of HIV-1 in humans. PLoS Genetics 5 e1000791

34. GudbjartssonDF

WaltersGB

ThorleifssonG

StefanssonH

HalldorssonBV

2008 Many sequence variants affecting diversity of adult human height. Nature Genetics 40 609 615

35. PritchardJK

PickrellJK

CoopG

2010 The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation. Current Biology 20 R208 R215

36. PritchardJK

Di RienzoA

2010 Adaptation – not by sweeps alone. Nature Reviews Genetics 11 665 667

37. HancockAM

WitonskyDB

EhlerE

Alkorta-AranburuG

BeallC

2010 Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proceedings of the National Academy of Science 107 Supplement 2 8924 8930

38. BartonNH

KeightleyPD

2002 Understanding quantitative genetic variation. Nature Reviews Genetics 3 11 21

39. Mitchell-OldsT

WillisJH

GoldsteinDB

2007 Which evolutionary processes influence natural genetic variation for phenotypic traits? Nature Reviews Genetics 8 845 856

40. StrumRA

2009 Molecular genetics of human pigmentation diversity. Human Molecular Genetics 18 R9 R17

41. WilliamsonSH

HubiszMJ

ClarkAG

PayseurBA

BustamanteCD

2007 Localizing recent adaptive evolution in the human genome. PLoS Genetics 3 e90

42. SabetiPC

VarillyP

FryB

LohuellerJ

HostetterE

2007 Genome-wide detection and characterization of positive selection in human populations. Nature 449 913 918

43. JohanssonA

GyllenstenU

2008 Identification of local selective sweeps in human populations since the exodus from Africa. Hereditas 145 126 137

44. LamasonRL

MohideenMPK

MestJR

WongAC

NortonHL

2005 SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans. Science 310 1782 1786

45. NortonHL

KittlesRA

ParraE

McKeigueP

MaoX

2007 Genetic Evidence for the Convergent Evolution of Light Skin in Europeans and East Asians. Molecular Biology and Evolution 24 710 722

46. SoejimaM

TachidaH

IshidaT

SanoA

KodaY

2006 Evidence for Recent Positive Selection at the Human AIM1 Locus in a European Population. Molecular Biology and Evolution 23 179 188

47. McEvoyB

BelezaS

ShriverMD

2006 The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model. Human Molecular Genetics 15 R176 R181

48. IzagirreN

GarciaI

JunqueraC

de la RuaC

AlonsoS

2006 A Scan for Signatures of Positive Selection in Candidate Loci for Skin Pigmentation in Humans. Molecular Biology and Evolution 23 1697 1706

49. LaoO

de GruijterJM

van DuijnK

NavarroA

KayserM

2007 Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms. Annals of Human Genetics 71 354 369

50. MylesS

SomelM

TangK

KelsoJ

StonekingM

2007 Identifying genes underlying skin pigmentation differences among human populations. Human Genetics 120 613 621

51. YoungJH

ChangYC

KimJD

ChretienJ

KlagMJ

2005 Differential Susceptibility to Hypertension is due to Selection during the Out-of-Africa Expansion. PLoS Genetics 1 e82

52. YoungJH

2007 Evolution of Blood Pressure Regulation in Humans. Current Hypertension Reports 9 13 18

53. ZhernakovaA

ElbersCC

FerwerdaB

RomanosJ

TrynkaG

2010 Evolutionary and Functional Analysis of Celiac Risk Loci Reveals SH2B3 as a Protective Factor against Bacterial Infection. American Journal of Human Genetics 86 970 977

54. KosiolC

VinařT

da FonsecaRR

HubiszMJ

BustamanteCD

2008 Patterns of positive selection in six mammalian genomes. PLoS Genetics 4 e1000144

55. BarreiroLB

Quintana-MurciL

2010 From evolutionary genetics to human immunology: how selection shapes host defence genes. Nature Reviews Genetics 11 17 30

56. HughesAL

NeiM

1988 Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335 167 170

57. TakahataN

SattaY

KleinJ

1992 Polymorphism and balancing selection at major histocompatibility complex loci. Genetics 130 925 938

58. PrugnolleF

ManicaA

CharpentierM

GuéganJF

GuernierV

2005 Pathogen-driven selection and worldwide HLA Class I diversity. Current Biology 15 1022 1027

59. SolbergOD

MackSJ

LancasterAK

SingleRM

TsaiY

2008 Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. Human Immunology 69 443 464

60. KwiatkowskiDP

2005 How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77 171 192

61. TishkoffSA

VarkonyiR

CahinhinanN

AbbesS

ArgyropoulosG

2001 Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293 455 462

62. HamblinMT

Di RienzoA

2000 Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. American Journal of Human Genetics 66 1669 1679

63. HamblinMT

ThompsonEE

Di RienzoA

2002 Complex signatures of natural selection at the Duffy blood group locus. American Journal of Human Genetics 70 369 383

64. OhashiJ

NakaI

PatarapotikulJ

HananantachaiH

BrittenhamG

2004 Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. American Journal of Human Genetics 74 1198 1208

65. WilderJA

HewettEK

GansnerME

2009 Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans. Molecular Biology and Evolution 26 2679 2687

66. SabetiPC

WalshE

SchaffnerSF

VarillyP

FryB

2005 The case for selection at CCR5-Δ32. PLoS Biology 3 e378

67. BamshadMJ

MummidiS

GonzalezE

AhujaSS

DunnDM

2002 A strong signature of balancing selection in the 5′ cis-regulatory region of CCR5. Proceedings of the National Academy of Sciences 99 10539 10544

68. BarreiroLB

Ben-AliM

QuachH

LavalG

PatinE

2009 Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genetics 5 e1000562

69. BernigT

TaylorJG

FosterCB

StaatsB

YeagerM

2004 Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection. Genes and Immunity 5 461 476

70. MukherjeeS

Sarkar-RoyN

WagenerDK

MajumderPP

2009 Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature. Proceedings of the National Academy of Sciences 106 7073 7078

71. HirayasuK

OhashiJ

TanakaH

KashiwaseK

OgawaA

2008 Evidence for natural selection on leukocyte immunoglobulin-like receptors for HLA class I in Northeast Asians. American Journal of Human Genetics 82 1075 1083

72. SeixasS

SurianoG

CarvalhoF

SerucaR

RochaJ

2007 Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2. Molecular Biology and Evolution 24 587 598

73. XueY

DalyA

YngvadottirB

LiuM

CoopG

2006 Spread of an inactive form of caspase-12 in humans is due to recent positive selection. American Journal of Human Genetics 78 659 670

74. VilchesC

ParhamP

2002 KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annual Reviews in Immunology 20 217 251

75. NormanPJ

Abi-RachedL

GendzekhadzeK

KorbelD

GleimerM

2007 Unusual selection on the KIR3DL/S1 natural killer cell receptor in Africans. Nature Genetics 39 1092 1099

76. GalvaniAP

SlatkinM

2003 Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele. Proceedings of the National Academy of Science 100 15276 15279

77. SiddiquiRA

SauermannU

AltmüllerJ

FritzerE

NothnagelM

2009 X chromosomal variation is associated with slow progression to AIDS in HIV-1-infected women. American Journal of Human Genetics 85 228 239

78. FumagalliM

PozzoliU

CagilaniR

ComiGP

RivaS

2009 Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. Journal of Experimental Medicine 206 1395 1408

79. RajagopalanS

LongEO

2005 Understanding how combinations of HLA and KIR genes influence disease. Journal of Experimental Medicine 201 1025 1029

80. NairRP

DuffinKC

HelmsC

DingJ

StuartPE

2009 Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappB pathways. Nature Genetics 41 199 204

81. ZhangXJ

HuangW

YangS