Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations

Roseann E. Peterson; Karoline Kuchenbaecker; Raymond K. Walters; Chia Yen Chen; Alice B. Popejoy; Sathish Periyasamy; Max Lam; Conrad Iyegbe; Rona J. Strawbridge; Leslie Brick; Caitlin E. Carey; Alicia R. Martin; Jacquelyn L. Meyers; Jinni Su; Junfang Chen; Alexis C. Edwards; Allan Kalungi; Nastassja Koen; Lerato Majara; Emanuel Schwarz; Jordan W. Smoller; Eli A. Stahl; Patrick F. Sullivan; Evangelos Vassos; Bryan Mowry; Miguel L. Prieto; Alfredo Cuellar-Barboza; Tim B. Bigdeli; Howard J. Edenberg; Hailiang Huang; Laramie E. Duncan

doi:10.1016/j.cell.2019.08.051

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations

Roseann E. Peterson^*, Karoline Kuchenbaecker, Raymond K. Walters, Chia Yen Chen, Alice B. Popejoy, Sathish Periyasamy, Max Lam, Conrad Iyegbe, Rona J. Strawbridge, Leslie Brick, Caitlin E. Carey, Alicia R. Martin, Jacquelyn L. Meyers, Jinni Su, Junfang Chen, Alexis C. Edwards, Allan Kalungi, Nastassja Koen, Lerato Majara, Emanuel SchwarzJordan W. Smoller, Eli A. Stahl, Patrick F. Sullivan, Evangelos Vassos, Bryan Mowry, Miguel L. Prieto, Alfredo Cuellar-Barboza, Tim B. Bigdeli, Howard J. Edenberg, Hailiang Huang, Laramie E. Duncan

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

361 Scopus citations

Abstract

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

Original language	English
Pages (from-to)	589-603
Number of pages	15
Journal	Cell
Volume	179
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2019.08.051
State	Published - 17 Oct 2019

Bibliographical note

Funding Information:
The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528, MH109539, MH109539, MH109536, MH109501, MH109514, MH109499, and MH109532. R.E.P. is supported by NIH grant K01 MH113848. K.K. is supported by Wellcome Trust grant 212360/Z/18/Z. R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health (5U01MH109539). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604. R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). A.R.M. is supported by NIH grant K99MH117229. M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116. H.H. is supported by NIH K01DK114379, R21AI139012, the Zhengxu & Ying He Foundation, and the Stanley Center for Psychiatric Research. L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences. P.F.S. was supported by the Swedish Research Council (Vetenskapsr?det, award D0886501), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307), and US NIMH (U01 MH109528 and R01 MH077139). P.F. Sullivan reports the following potentially competing financial interests. Current: Lundbeck (advisory committee, grant recipient). Past three years: Pfizer (scientific advisory board).

Funding Information:
The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528 , MH109539 , MH109539 , MH109536 , MH109501 , MH109514 , MH109499 , and MH109532 . R.E.P. is supported by NIH grant K01 MH113848 . K.K. is supported by Wellcome Trust grant 212360/Z/18/Z . R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health ( 5U01MH109539 ). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604 . R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship ( MR/S003061/1 ). A.R.M. is supported by NIH grant K99MH117229 . M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116 . H.H. is supported by NIH K01DK114379 , R21AI139012 , the Zhengxu & Ying He Foundation , and the Stanley Center for Psychiatric Research . L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences . P.F.S. was supported by the Swedish Research Council (Vetenskapsrådet, award D0886501 ), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307 ), and US NIMH ( U01 MH109528 and R01 MH077139 ).

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

GWAS
admixed populations
ancestry
complex disease
cross-ancestry
diversity
population genetics
psychiatry
trans-ancestry
trans-ethnic

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10.1016/j.cell.2019.08.051

Cite this

Peterson, R. E., Kuchenbaecker, K., Walters, R. K., Chen, C. Y., Popejoy, A. B., Periyasamy, S., Lam, M., Iyegbe, C., Strawbridge, R. J., Brick, L., Carey, C. E., Martin, A. R., Meyers, J. L., Su, J., Chen, J., Edwards, A. C., Kalungi, A., Koen, N., Majara, L., ... Duncan, L. E. (2019). Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations. Cell, 179(3), 589-603. https://doi.org/10.1016/j.cell.2019.08.051

@article{c5c8cfa7dcf841919c1705c13e52210b,

title = "Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations",

abstract = "Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.",

keywords = "GWAS, admixed populations, ancestry, complex disease, cross-ancestry, diversity, population genetics, psychiatry, trans-ancestry, trans-ethnic, admixed populations, ancestry, complex disease, cross-ancestry, diversity, GWAS, population genetics, psychiatry, trans-ancestry, trans-ethnic",

author = "Peterson, {Roseann E.} and Karoline Kuchenbaecker and Walters, {Raymond K.} and Chen, {Chia Yen} and Popejoy, {Alice B.} and Sathish Periyasamy and Max Lam and Conrad Iyegbe and Strawbridge, {Rona J.} and Leslie Brick and Carey, {Caitlin E.} and Martin, {Alicia R.} and Meyers, {Jacquelyn L.} and Jinni Su and Junfang Chen and Edwards, {Alexis C.} and Allan Kalungi and Nastassja Koen and Lerato Majara and Emanuel Schwarz and Smoller, {Jordan W.} and Stahl, {Eli A.} and Sullivan, {Patrick F.} and Evangelos Vassos and Bryan Mowry and Prieto, {Miguel L.} and Alfredo Cuellar-Barboza and Bigdeli, {Tim B.} and Edenberg, {Howard J.} and Hailiang Huang and Duncan, {Laramie E.}",

note = "Funding Information: The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528, MH109539, MH109539, MH109536, MH109501, MH109514, MH109499, and MH109532. R.E.P. is supported by NIH grant K01 MH113848. K.K. is supported by Wellcome Trust grant 212360/Z/18/Z. R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health (5U01MH109539). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604. R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). A.R.M. is supported by NIH grant K99MH117229. M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116. H.H. is supported by NIH K01DK114379, R21AI139012, the Zhengxu & Ying He Foundation, and the Stanley Center for Psychiatric Research. L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences. P.F.S. was supported by the Swedish Research Council (Vetenskapsr?det, award D0886501), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307), and US NIMH (U01 MH109528 and R01 MH077139). P.F. Sullivan reports the following potentially competing financial interests. Current: Lundbeck (advisory committee, grant recipient). Past three years: Pfizer (scientific advisory board). Funding Information: The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528 , MH109539 , MH109539 , MH109536 , MH109501 , MH109514 , MH109499 , and MH109532 . R.E.P. is supported by NIH grant K01 MH113848 . K.K. is supported by Wellcome Trust grant 212360/Z/18/Z . R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health ( 5U01MH109539 ). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604 . R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship ( MR/S003061/1 ). A.R.M. is supported by NIH grant K99MH117229 . M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116 . H.H. is supported by NIH K01DK114379 , R21AI139012 , the Zhengxu & Ying He Foundation , and the Stanley Center for Psychiatric Research . L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences . P.F.S. was supported by the Swedish Research Council (Vetenskapsr{\aa}det, award D0886501 ), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307 ), and US NIMH ( U01 MH109528 and R01 MH077139 ). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = oct,

day = "17",

doi = "10.1016/j.cell.2019.08.051",

language = "English",

volume = "179",

pages = "589--603",

journal = "Cell",

issn = "0092-8674",

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Peterson, RE, Kuchenbaecker, K, Walters, RK, Chen, CY, Popejoy, AB, Periyasamy, S, Lam, M, Iyegbe, C, Strawbridge, RJ, Brick, L, Carey, CE, Martin, AR, Meyers, JL, Su, J, Chen, J, Edwards, AC, Kalungi, A, Koen, N, Majara, L, Schwarz, E, Smoller, JW, Stahl, EA, Sullivan, PF, Vassos, E, Mowry, B, Prieto, ML, Cuellar-Barboza, A, Bigdeli, TB, Edenberg, HJ, Huang, H & Duncan, LE 2019, 'Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations', Cell, vol. 179, no. 3, pp. 589-603. https://doi.org/10.1016/j.cell.2019.08.051

TY - JOUR

T1 - Genome-wide Association Studies in Ancestrally Diverse Populations

T2 - Opportunities, Methods, Pitfalls, and Recommendations

AU - Peterson, Roseann E.

AU - Kuchenbaecker, Karoline

AU - Walters, Raymond K.

AU - Chen, Chia Yen

AU - Popejoy, Alice B.

AU - Periyasamy, Sathish

AU - Lam, Max

AU - Iyegbe, Conrad

AU - Strawbridge, Rona J.

AU - Brick, Leslie

AU - Carey, Caitlin E.

AU - Martin, Alicia R.

AU - Meyers, Jacquelyn L.

AU - Su, Jinni

AU - Chen, Junfang

AU - Edwards, Alexis C.

AU - Kalungi, Allan

AU - Koen, Nastassja

AU - Majara, Lerato

AU - Schwarz, Emanuel

AU - Smoller, Jordan W.

AU - Stahl, Eli A.

AU - Sullivan, Patrick F.

AU - Vassos, Evangelos

AU - Mowry, Bryan

AU - Prieto, Miguel L.

AU - Cuellar-Barboza, Alfredo

AU - Bigdeli, Tim B.

AU - Edenberg, Howard J.

AU - Huang, Hailiang

AU - Duncan, Laramie E.

N1 - Funding Information: The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528, MH109539, MH109539, MH109536, MH109501, MH109514, MH109499, and MH109532. R.E.P. is supported by NIH grant K01 MH113848. K.K. is supported by Wellcome Trust grant 212360/Z/18/Z. R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health (5U01MH109539). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604. R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). A.R.M. is supported by NIH grant K99MH117229. M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116. H.H. is supported by NIH K01DK114379, R21AI139012, the Zhengxu & Ying He Foundation, and the Stanley Center for Psychiatric Research. L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences. P.F.S. was supported by the Swedish Research Council (Vetenskapsr?det, award D0886501), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307), and US NIMH (U01 MH109528 and R01 MH077139). P.F. Sullivan reports the following potentially competing financial interests. Current: Lundbeck (advisory committee, grant recipient). Past three years: Pfizer (scientific advisory board). Funding Information: The authors acknowlesdge the support and helpful discussions with many members in the Psychiatric Genomics Consortium (PGC), which is supported by the National Institutes of Health (NIH) grants U01 MH109528 , MH109539 , MH109539 , MH109536 , MH109501 , MH109514 , MH109499 , and MH109532 . R.E.P. is supported by NIH grant K01 MH113848 . K.K. is supported by Wellcome Trust grant 212360/Z/18/Z . R.K.W. is supported by the Stanley Center for Psychiatric Research and the National Institutes of Health ( 5U01MH109539 ). A.B.P. is supported by a postdoctoral fellowship from the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). C.I. is supported by the NARSAD Young Investigator Award grant 22604 . R.J.S. is supported by a UKRI Innovation-HDR-UK Fellowship ( MR/S003061/1 ). A.R.M. is supported by NIH grant K99MH117229 . M.L.P. is supported in part by grant CONICYT FONDECYT 1181365 and grant CONICYT FONDEF ID1910116 . H.H. is supported by NIH K01DK114379 , R21AI139012 , the Zhengxu & Ying He Foundation , and the Stanley Center for Psychiatric Research . L.D. was supported by UL1 TR001085 and the Stanford Department of Psychiatry and Behavioral Sciences . P.F.S. was supported by the Swedish Research Council (Vetenskapsrådet, award D0886501 ), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement number 610307 ), and US NIMH ( U01 MH109528 and R01 MH077139 ). Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/10/17

Y1 - 2019/10/17

N2 - Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

AB - Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

KW - GWAS

KW - admixed populations

KW - ancestry

KW - complex disease

KW - cross-ancestry

KW - diversity

KW - population genetics

KW - psychiatry

KW - trans-ancestry

KW - trans-ethnic

KW - admixed populations

KW - ancestry

KW - complex disease

KW - cross-ancestry

KW - diversity

KW - GWAS

KW - population genetics

KW - psychiatry

KW - trans-ancestry

KW - trans-ethnic

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U2 - 10.1016/j.cell.2019.08.051

DO - 10.1016/j.cell.2019.08.051

M3 - Review article

C2 - 31607513

AN - SCOPUS:85073429171

SN - 0092-8674

VL - 179

SP - 589

EP - 603

JO - Cell

JF - Cell

IS - 3

ER -

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations

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Keywords

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