Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.
While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a f...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001371&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849333091487711232 |
|---|---|
| author | Bogdan Pasaniuc Noah Zaitlen Guillaume Lettre Gary K Chen Arti Tandon W H Linda Kao Ingo Ruczinski Myriam Fornage David S Siscovick Xiaofeng Zhu Emma Larkin Leslie A Lange L Adrienne Cupples Qiong Yang Ermeg L Akylbekova Solomon K Musani Jasmin Divers Joe Mychaleckyj Mingyao Li George J Papanicolaou Robert C Millikan Christine B Ambrosone Esther M John Leslie Bernstein Wei Zheng Jennifer J Hu Regina G Ziegler Sarah J Nyante Elisa V Bandera Sue A Ingles Michael F Press Stephen J Chanock Sandra L Deming Jorge L Rodriguez-Gil Cameron D Palmer Sarah Buxbaum Lynette Ekunwe Joel N Hirschhorn Brian E Henderson Simon Myers Christopher A Haiman David Reich Nick Patterson James G Wilson Alkes L Price |
| author_facet | Bogdan Pasaniuc Noah Zaitlen Guillaume Lettre Gary K Chen Arti Tandon W H Linda Kao Ingo Ruczinski Myriam Fornage David S Siscovick Xiaofeng Zhu Emma Larkin Leslie A Lange L Adrienne Cupples Qiong Yang Ermeg L Akylbekova Solomon K Musani Jasmin Divers Joe Mychaleckyj Mingyao Li George J Papanicolaou Robert C Millikan Christine B Ambrosone Esther M John Leslie Bernstein Wei Zheng Jennifer J Hu Regina G Ziegler Sarah J Nyante Elisa V Bandera Sue A Ingles Michael F Press Stephen J Chanock Sandra L Deming Jorge L Rodriguez-Gil Cameron D Palmer Sarah Buxbaum Lynette Ekunwe Joel N Hirschhorn Brian E Henderson Simon Myers Christopher A Haiman David Reich Nick Patterson James G Wilson Alkes L Price |
| author_sort | Bogdan Pasaniuc |
| collection | DOAJ |
| description | While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations. |
| format | Article |
| id | doaj-art-e78b675e8c4a46afaeac1231b3939d8c |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e78b675e8c4a46afaeac1231b3939d8c2025-08-20T03:45:59ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-04-0174e100137110.1371/journal.pgen.1001371Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.Bogdan PasaniucNoah ZaitlenGuillaume LettreGary K ChenArti TandonW H Linda KaoIngo RuczinskiMyriam FornageDavid S SiscovickXiaofeng ZhuEmma LarkinLeslie A LangeL Adrienne CupplesQiong YangErmeg L AkylbekovaSolomon K MusaniJasmin DiversJoe MychaleckyjMingyao LiGeorge J PapanicolaouRobert C MillikanChristine B AmbrosoneEsther M JohnLeslie BernsteinWei ZhengJennifer J HuRegina G ZieglerSarah J NyanteElisa V BanderaSue A InglesMichael F PressStephen J ChanockSandra L DemingJorge L Rodriguez-GilCameron D PalmerSarah BuxbaumLynette EkunweJoel N HirschhornBrian E HendersonSimon MyersChristopher A HaimanDavid ReichNick PattersonJames G WilsonAlkes L PriceWhile genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001371&type=printable |
| spellingShingle | Bogdan Pasaniuc Noah Zaitlen Guillaume Lettre Gary K Chen Arti Tandon W H Linda Kao Ingo Ruczinski Myriam Fornage David S Siscovick Xiaofeng Zhu Emma Larkin Leslie A Lange L Adrienne Cupples Qiong Yang Ermeg L Akylbekova Solomon K Musani Jasmin Divers Joe Mychaleckyj Mingyao Li George J Papanicolaou Robert C Millikan Christine B Ambrosone Esther M John Leslie Bernstein Wei Zheng Jennifer J Hu Regina G Ziegler Sarah J Nyante Elisa V Bandera Sue A Ingles Michael F Press Stephen J Chanock Sandra L Deming Jorge L Rodriguez-Gil Cameron D Palmer Sarah Buxbaum Lynette Ekunwe Joel N Hirschhorn Brian E Henderson Simon Myers Christopher A Haiman David Reich Nick Patterson James G Wilson Alkes L Price Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. PLoS Genetics |
| title | Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. |
| title_full | Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. |
| title_fullStr | Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. |
| title_full_unstemmed | Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. |
| title_short | Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium. |
| title_sort | enhanced statistical tests for gwas in admixed populations assessment using african americans from care and a breast cancer consortium |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001371&type=printable |
| work_keys_str_mv | AT bogdanpasaniuc enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT noahzaitlen enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT guillaumelettre enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT garykchen enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT artitandon enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT whlindakao enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT ingoruczinski enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT myriamfornage enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT davidssiscovick enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT xiaofengzhu enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT emmalarkin enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT lesliealange enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT ladriennecupples enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT qiongyang enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT ermeglakylbekova enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT solomonkmusani enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT jasmindivers enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT joemychaleckyj enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT mingyaoli enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT georgejpapanicolaou enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT robertcmillikan enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT christinebambrosone enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT esthermjohn enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT lesliebernstein enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT weizheng enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT jenniferjhu enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT reginagziegler enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT sarahjnyante enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT elisavbandera enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT sueaingles enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT michaelfpress enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT stephenjchanock enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT sandraldeming enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT jorgelrodriguezgil enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT camerondpalmer enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT sarahbuxbaum enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT lynetteekunwe enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT joelnhirschhorn enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT brianehenderson enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT simonmyers enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT christopherahaiman enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT davidreich enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT nickpatterson enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT jamesgwilson enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium AT alkeslprice enhancedstatisticaltestsforgwasinadmixedpopulationsassessmentusingafricanamericansfromcareandabreastcancerconsortium |