The Future of Genomic Studies Must Be Globally Representative: Perspectives from PAGE

Annual Review of Genomics and Human Genetics

Volumn 20, Issue , 2019, Pages 181-200

  Bien, Stephanie A ^a   Wojcik, Genevieve L ^b   Hodonsky, Chani J ^c   Gignoux, Christopher R ^d   Cheng, Iona ^e   Matise, Tara C ^f   Peters, Ulrike ^a   Kenny, Eimear E ^g   North, Kari E ^c  

^a Fred Hutchinson Cancer Research Center   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c University of North Carolina at Chapel Hill   (United States)

^d UNIVERSITY OF COLORADO   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f RUTGERS UNIVERSITY   (United States)

^g MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

diversity; fine mapping; genomics; multiethnic; PAGE; transethnic

Indexed keywords

GENETIC EPIDEMIOLOGY; GENETIC RISK; GENOMICS; HUMAN; META ANALYSIS; POPULATION RESEARCH; PREDICTION; REVIEW; ANCESTRY GROUP; ETHNIC GROUP; FACTUAL DATABASE; GENETIC VARIATION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMAN GENETICS; HUMAN GENOME; METAGENOMICS; MOLECULAR EPIDEMIOLOGY; PHENOTYPE; STATISTICAL BIAS;

BIAS; CONTINENTAL POPULATION GROUPS; DATABASES, FACTUAL; ETHNIC GROUPS; GENETIC VARIATION; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMAN GENETICS; HUMANS; METAGENOMICS; MOLECULAR EPIDEMIOLOGY; PHENOTYPE;

EID: 85071718806     PISSN: 15278204     EISSN: 1545293X     Source Type: Book Series    
DOI: 10.1146/annurev-genom-091416-035517     Document Type: Review

References (127)

1. 1000 Genomes Proj. Consort. 2015. A global reference for human genetic variation. Nature 526:68-74
2. Adashi EY, Walters LB, Menikoff JA. 2018. The Belmont Report at 40: reckoning with time. Am. J. Public Health 108:1345-48
3. ARIC Investig. 1989. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am. J. Epidemiol. 129:687-702
4. AveryCL, Sethupathy P,Buyske S,HeQ,Lin D-Y, et al. 2012. Fine-mapping and initial characterization of QT interval loci in African Americans. PLOS Genet. 8:e1002870
5. Avery CL,Wassel CL, Richard MA, Highland HM, Bien S, et al. 2017. Fine mapping of QT interval regions in global populations refines previously identified QT interval loci and identifies signals unique to African and Hispanic descent populations. Heart Rhythm 14:572-80
6. Baharian S, Barakatt M, Gignoux CR, Shringarpure S, Errington J, et al. 2016. The great migration and African-American genomic diversity. PLOS Genet. 12:e1006059
7. Bai H, Guo X, Narisu N, Lan T, Wu Q, et al. 2018. Whole-genome sequencing of 175 Mongolians uncovers population-specific genetic architecture and gene flow throughout North and East Asia. Nat. Genet. 50:1696-704
8. Ball TB, Ji H, Kimani J, McLaren P, Marlin C, et al. 2007. Polymorphisms in IRF-1 associated with resistance to HIV-1 infection in highly exposed uninfected Kenyan sex workers. AIDS 21:1091-101
9. Baran Y,Pasaniuc B, Sankararaman S,Torgerson DG,Gignoux C, et al. 2012. Fast and accurate inference of local ancestry in Latino populations. Bioinformatics 28:1359-67
10. Battle A,Mostafavi S, Zhu X, Potash JB,Weissman MM, et al. 2014. Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res. 24:14-24
11. Belbin GM,Nieves-Colon MA,Kenny EE, Moreno-Estrada A, Gignoux CR. 2018. Genetic diversity in populations across Latin America: implications for population and medical genetic studies. Curr. Opin. Genet. Dev. 53:98-104
12. Belbin GM, Odgis J, Sorokin EP, Yee M-C, Kohli S, et al. 2017. Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system. eLife 6:e25060
13. Bien SA, Pankow JS, Haessler J, Lu YN, Pankratz N, et al. 2017. Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture Using Genomics and Epidemiology (PAGE) consortium. Diabetologia 60:2384-98
14. Bien SA,Wojcik GL, Zubair N, Gignoux CR, Martin AR, et al. 2016. Strategies for enriching variant coverage in candidate disease loci on a multiethnic genotyping array. PLOS ONE 11:e0167758
15. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, et al. 2002. Multi-ethnic study of atherosclerosis: objectives and design. Am. J. Epidemiol. 156:871-81
16. Bonham VL, Green ED, Perez-Stable EJ. 2018. Examining how race, ethnicity, and ancestry data are used in biomedical research. JAMA 320:1533-34
17. Boyle EA, Li YI, Pritchard JK. 2017. An expanded view of complex traits: from polygenic to omnigenic. Cell 169:1177-86
18. Bryc K, Durand EY, Macpherson JM, Reich D, Mountain JL. 2015. The genetic ancestry of African Americans, Latinos, and European Americans across the United States. Am. J. Hum. Genet. 96:37-53
19. Bustamante CD, Burchard EG, De La Vega FM. 2011. Genomics for the world. Nature 475:163-65
20. Campbell MC, Tishkoff SA. 2008. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genom. Hum. Genet. 9:403-33
21. Carlson CS, Eberle MA, Rieder MJ, Yi Q, Kruglyak L, Nickerson DA. 2004. Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am. J. Hum. Genet. 74:106-20
22. Carnethon MR, Pu J, Howard G, Albert MA, Anderson CAM, et al. 2017. Cardiovascular health in African Americans: a scientific statement from the American Heart Association. Circulation 136:e393-423
23. Carty CL, Spencer KL, Setiawan VW, Fernandez-Rhodes L, Malinowski J, et al. 2013. Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture Using Genomics and Epidemiology (PAGE) study. Hum. Reprod. 28:1695-706
24. Caswell-Jin JL, Gupta T, Hall E, Petrovchich IM, Mills MA, et al. 2018. Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk. Genet.Med. 20:234-39
25. Cent. Dis. Control Prev. 2017. National diabetes statistics report, 2017. Rep., Cent. Dis. Control Prev., Atlanta. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
26. Check Hayden E. 2015. Racial bias continues to haunt NIH grants. Nature 527:286-87
27. Cheng C-Y, Kao WHL, Patterson N, Tandon A, Haiman CA, et al. 2009. Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. PLOS Genet. 5:e1000490
28. Cheng I, Caberto CP, Lum-Jones A, Seifried A,Wilkens LR, et al. 2011. Type 2 diabetes risk variants and colorectal cancer risk: the multiethnic cohort and PAGE studies. Gut 60:1703-11
29. Colic A, Alessandrini M, Pepper MS. 2015. Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine. Drug Metab. Rev. 47:111-23
30. Conomos MP, Laurie CA, Stilp AM, Gogarten SM, McHugh CP, et al. 2016. Genetic diversity and association studies in US Hispanic/Latino populations: applications in theHispanic Community Health Study/Study of Latinos. Am. J. Hum. Genet. 98:165-84
31. Conomos MP, Miller MB, Thornton TA. 2015. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness. Genet. Epidemiol. 39:276-93
32. ConomosMP, Reiner AP,Weir BS, Thornton TA. 2016. Model-free estimation of recent genetic relatedness. Am. J. Hum. Genet. 98:127-48
33. Deelen P, Menelaou A, van Leeuwen EM, Kanterakis A, van Dijk F, et al. 2014. Improved imputation quality of low-frequency and rare variants in European samples using the "Genome of theNetherlands." Eur. J. Hum. Genet. 22:1321-26
34. Diabetes Genet. Replication Meta-Anal. (DIAGRAM) Consort., Asian Genet. Epidemiol. Netw. Type 2 Diabetes (AGEN-T2D) Consort., South Asian Type 2 Diabetes (SAT2D) Consort.,Mex. Am. Type 2 Diabetes (MAT2D) Consort., Type 2 Diabetes Genet. Explor.Next-Gener. Seq. Multi-Ethnic Samples (T2D-GENES) Consort., et al. 2014. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet. 46:234-44
35. Dumitrescu L, Carty CL, Taylor K, Schumacher FR,Hindorff LA, et al. 2011. Genetic determinants of lipid traits in diverse populations from the Population Architecture Using Genomics and Epidemiology (PAGE) study. PLOS Genet. 7:e1002138
36. Fernandez-Rhodes L, Gong J, Haessler J, Franceschini N, Graff M, et al. 2017. Trans-ethnic finemapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture Using Genomics and Epidemiology (PAGE) study reveals evidence for multiple signals at established loci. Hum. Genet. 136:771-800
37. Fesinmeyer MD, Meigs JB, North KE, Schumacher FR, B uzkova P, et al. 2013. Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture Using Genomics and Epidemiology (PAGE) study. BMC Med. Genet. 14:98
38. Fesinmeyer MD, North KE, Ritchie MD, Lim U, Franceschini N, et al. 2013. Genetic risk factors for BMI and obesity in an ethnically diverse population: results from the Population Architecture Using Genomics and Epidemiology (PAGE) study. Obesity 21:835-46
39. Franceschini N, Carty CL, Lu Y, Tao R, Sung YJ, et al. 2016. Variant discovery and fine mapping of genetic loci associated with blood pressure traits in Hispanics and African Americans. PLOS ONE 11:e0164132
40. Franceschini N, Shara NM,Wang H, Voruganti VS, Laston S, et al. 2012. The association of genetic variants of type 2 diabetes with kidney function. Kidney Int. 82:220-25
41. Freedman BI, Limou S, Ma L, Kopp JB. 2018. APOL1-associated nephropathy: a key contributor to racial disparities in CKD. Am. J. Kidney Dis. 72:S8-16
42. Fu W, O'Connor TD, Jun G, Kang HM, Abecasis G, et al. 2013. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493:216-20
43. Gamazon ER, Wheeler HE, Shah KP, Mozaffari SV, Aquino-Michaels K, et al. 2015. A genebased association method for mapping traits using reference transcriptome data. Nat. Genet. 47:1091-98
44. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, et al. 2010. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329:841-45
45. Gignoux C, Sorokin E,Wojcik G, Belbin G, Bien S, et al. 2018. The global landscape of pharmacogenomic variation. Paper presented at the Annual Meeting of the American Society of Human Genetics, San Diego, CA, Oct. 16-20
46. Gignoux CR,Torgerson DG,Pino-Yanes M,Uricchio LH,Galanter J, et al. 2019.An admixturemapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos. J. Allergy Clin. Immunol. 143:957-69
47. Gong J, Schumacher F, Lim U,Hindorff LA, Haessler J, et al. 2013. Fine mapping and identification of BMI loci in African Americans. Am. J. Hum. Genet. 93:661-71
48. Gravel S, Henn BM, Gutenkunst RN, Indap AR, Marth GT, et al. 2011. Demographic history and rare allele sharing among human populations. PNAS 108:11983-88
49. GTEx Consort. 2013. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45:580-85
50. Gurdasani D, Carstensen T,Tekola-Ayele F, Pagani L,Tachmazidou I, et al. 2015. The African genome variation project shapes medical genetics in Africa. Nature 517:327-32
51. Gusev A, Ko A, Shi H, Bhatia G, Chung W, et al. 2016. Integrative approaches for large-scale transcriptome-wide association studies. Nat. Genet. 48:245-52
52. H3Africa Consort. 2014. Enabling the genomic revolution in Africa. Science 344:1346-48
53. Haiman CA, Fesinmeyer MD, Spencer KL, Buzkova P, Voruganti VS, et al. 2012. Consistent directions of effect for established type 2 diabetes risk variants across populations: the Population Architecture Using Genomics and Epidemiology (PAGE) consortium. Diabetes 61:1642-47
54. Hellenthal G, Busby GBJ, Band G,Wilson JF, Capelli C, et al. 2014. A genetic atlas of human admixture history. Science 343:747-51
55. Henn BM, Botigue LR, Peischl S, Dupanloup I, Lipatov M, et al. 2016. Distance from sub-Saharan Africa predicts mutational load in diverse human genomes. PNAS 113:E440-49
56. Hindorff LA, Bonham VL, Brody LC, Ginoza MEC, Hutter CM, et al. 2018. Prioritizing diversity in human genomics research. Nat. Rev. Genet. 19:175-85
57. Hindorff LA, Bonham VL, Ohno-Machado L. 2018. Enhancing diversity to reduce health information disparities and build an evidence base for genomic medicine. Pers.Med. 15:403-12
58. Hodonsky CJ, Jain D, Schick UM,Morrison JV, Brown L, et al. 2017. Genome-wide association study of red blood cell traits in Hispanics/Latinos: the Hispanic Community Health Study/Study of Latinos. PLOS Genet. 13:e1006760
59. Hormozdiari F, Kostem E, Kang EY, Pasaniuc B, Eskin E. 2014. Identifying causal variants at loci with multiple signals of association. Genetics 198:497-508
60. Illumina. 2019. Human consortia. Illumina. https://www.illumina.com/science/consortia/humanconsortia. html
61. Int. HapMap Consort. 2003. The International HapMap Project. Nature 426:789-96
62. JennesW, Verheyden S, Demanet C, Adje-Toure CA, Vuylsteke B, et al. 2006. Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands. J. Immunol. 177:6588-92
63. Johnston HR, Hu Y-J, Gao J, O'Connor TD, Abecasis GR, et al. 2017. Identifying tagging SNPs for African specific genetic variation from the African diaspora genome. Sci. Rep. 7:46398
64. Kallwitz ER, Daviglus ML, Allison MA, Emory KT, Zhao L, et al. 2015. Prevalence of suspected nonalcoholic fatty liver disease in Hispanic/Latino individuals differs by heritage. Clin. Gastroenterol. Hepatol. 13:569-76
65. Kao WHL, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, et al. 2008. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat. Genet. 40:1185-92
66. Keys KL,Mak ACY, White MJ, Eckalbar W, Dahl AJ, et al. 2019. On the cross-population portability of gene expression prediction models. bioRxiv 552042. https://doi.org/10.1101/552042
67. Khera AV, Chaffin M, Aragam KG,Haas ME, Roselli C, et al. 2018. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenicmutations. Nat.Genet. 50:1219-24
68. KichaevG,Roytman M, Johnson R, Eskin E, Lindstrom S, et al. 2017. Improved methods formulti-trait fine mapping of pleiotropic risk loci. Bioinformatics 33:248-55
69. Klein K, Lang T, Saussele T, Barbosa-Sicard E, SchunckW-H, et al. 2005. Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet. Genom. 15:861-73
70. Ko W-Y, Rajan P, Gomez F, Scheinfeldt L, An P, et al. 2013. Identifying Darwinian selection acting on different human APOL1 variants among diverse African populations. Am. J. Hum. Genet. 93:54-66
71. Kocarnik JM, Richard M, Graff M, Haessler J, Bien S, et al. 2018. Discovery, fine-mapping, and conditional analyses of genetic variants associated with c-reactive protein in multiethnic populations using the Metabochip in the Population Architecture Using Genomics and Epidemiology (PAGE) study. Hum. Mol. Genet. 27:2940-53
72. Kolonel LN, Henderson BE, Hankin JH, Nomura AM,Wilkens LR, et al. 2000. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am. J. Epidemiol. 151:346-57
73. Kwiatkowski DP. 2005.Howmalaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet. 77:171-92
74. Lama J, PlanellesV. 2007. Host factors influencing susceptibility toHIV infection and AIDS progression. Retrovirology 4:52
75. Lim U, Wilkens LR, Monroe KR, Caberto C, Tiirikainen M, et al. 2012. Susceptibility variants for obesity and colorectal cancer risk: the multiethnic cohort and PAGE studies. Int. J. Cancer 131:E1038-43
76. Lin D-Y, Tao R, Kalsbeek WD, Zeng D, Gonzalez F, et al. 2014. Genetic association analysis under complex survey sampling: the Hispanic Community Health Study/Study of Latinos. Am. J.Hum. Genet. 95:675-88
77. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. 2009. Finding the missing heritability of complex diseases. Nature 461:747-53
78. Manrai AK, Funke BH, Rehm HL, Olesen MS, Maron BA, et al. 2016. Genetic misdiagnoses and the potential for health disparities. N. Engl. J.Med. 375:655-65
79. Maples BK, Gravel S, Kenny EE, Bustamante CD. 2013. RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference. Am. J. Hum. Genet. 93:278-88
80. Marcus JH, Novembre J. 2017. Visualizing the geography of genetic variants. Bioinformatics 33:594-95
81. Martin AR,Gignoux CR,Walters RK,Wojcik GL, Neale BM, et al. 2017. Human demographic history impacts genetic risk prediction across diverse populations. Am. J. Hum. Genet. 100:635-49
82. Mathias RA, Taub MA, Gignoux CR, Fu W,Musharoff S, et al. 2016. A continuum of admixture in the Western Hemisphere revealed by the African diaspora genome. Nat. Commun. 7:12522
83. McCarthy S, Das S, Kretzschmar W, Delaneau O,Wood AR, et al. 2016. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48:1279-83
84. Mills MC, Rahal C. 2019. A scientometric review of genome-wide association studies. Commun. Biol. 2:9
85. Miwa S, Fujii H. 1996. Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: tabulation of mutant enzymes. Am. J. Hematol. 51:122-32
86. Moreno-Estrada A, Gignoux CR, Fernandez-Lopez JC, Zakharia F, Sikora M, et al. 2014. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344:1280-85
87. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, et al. 2012. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44:981-90
88. Nadkarni GN, Gignoux CR, Sorokin EP, Daya M, Rahman R, et al. 2018. Worldwide frequencies of APOL1 renal risk variants.N. Engl. J. Med. 379:2571-72
89. Need AC,Goldstein DB. 2009. Next generation disparities in human genomics: concerns and remedies. Trends Genet. 25:489-94
90. Newman LA. 2015. Disparities in breast cancer and African ancestry: a global perspective. Breast J. 21:133-39
91. Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME,Cox NJ. 2010.Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLOS Genet. 6:e1000888
92. Park SL, Fesinmeyer MD,Timofeeva M, Caberto CP,Kocarnik JM, et al. 2014. Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia. J. Natl. Cancer Inst. 106:dju061
93. Parsa A, Kao WHL, Xie D, Astor BC, Li M, et al. 2013. APOL1 risk variants, race, and progression of chronic kidney disease. N. Engl. J.Med. 369:2183-96
94. Popejoy AB, Fullerton SM. 2016. Genomics is failing on diversity. Nature 538:161-64
95. Popejoy AB, Ritter DI, Crooks K, Currey E, Fullerton SM, et al. 2018. The clinical imperative for inclusivity: race, ethnicity, and ancestry (REA) in genomics. Hum. Mutat. 39:1713-20
96. Price AL, Patterson NJ, Plenge RM,WeinblattME, Shadick NA, Reich D. 2006. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38:904-9
97. Price AL, Zaitlen NA, Reich D, Patterson N. 2010. New approaches to population stratification in genome-wide association studies. Nat. Rev. Genet. 11:459-63
98. Roadmap Epigenom. Consort., Kundaje A, Meuleman W, Ernst J, Bilenky M, et al. 2015. Integrative analysis of 111 reference human epigenomes. Nature 518:317-30
99. Rotimi CN, Bentley AR,Doumatey AP,Chen G, Shriner D, Adeyemo A. 2017. The genomic landscape of African populations in health and disease. Hum. Mol. Genet. 26:R225-36
100. Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, et al. 1995. Natural selection of hemi-and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376:246-49
101. Saab S, Manne V, Nieto J, Schwimmer JB, Chalasani NP. 2016. Nonalcoholic fatty liver disease in Latinos. Clin. Gastroenterol. Hepatol. 14:5-12
102. Saran R, Robinson B, Abbott KC, Agodoa LYC, Albertus P, et al. 2017. US Renal Data System 2016 Annual Data Report: epidemiology of kidney disease in the United States. Am. J. Kidney Dis. 69(Suppl. 1):A7-8
103. Saunders MA, Hammer MF, Nachman MW. 2002. Nucleotide variability at g6pd and the signature of malarial selection in humans. Genetics 162:1849-61
104. Schneider ALC, Lazo M, Selvin E, Clark JM. 2014. Racial differences in nonalcoholic fatty liver disease in the U.S. population. Obesity 22:292-99
105. Sempos CT,Bild DE, ManolioTA. 1999. Overview of the JacksonHeart Study: a study of cardiovascular diseases in African American men and women. Am. J.Med. Sci. 317:142-46
106. Setiawan VW, Haessler J, Schumacher F, Cote ML, Deelman E, et al. 2012. HNF1B and endometrial cancer risk: results from the PAGE study. PLOS ONE 7:e30390
107. Shriner D. 2017. Overview of admixture mapping. Curr. Protoc. Hum. Genet. 94:1.23.1-8
108. Simons YB, Bullaughey K, Hudson RR, Sella G. 2018. A population genetic interpretation of GWAS findings for human quantitative traits. PLOS Biol. 16:e2002985
109. Sofer T, Baier LJ, Browning SR, Thornton TA, Talavera GA, et al. 2017. Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits. PLOS ONE 12:e0188400
110. Sorlie PD, Aviles-Santa LM,Wassertheil-Smoller S, Kaplan RC, Daviglus ML, et al. 2010. Design and implementation of the Hispanic Community Health Study/Study of Latinos. Ann. Epidemiol. 20:629-41
111. Spencer KL, Malinowski J, Carty CL, Franceschini N, Fernandez-Rhodes L, et al. 2013. Genetic variation and reproductive timing: African American women from the Population Architecture Using Genomics and Epidemiology (PAGE) study. PLOS ONE 8:e55258
112. Su Y-R, Di C, Bien SA, Huang L, Dong X, et al. 2018. A mixed-effects model for powerful association tests in integrative functional genomics: an application to a large-scale genome-wide association study of colorectal cancer. Am. J. Hum. Genet. 102:904-19
113. SwartM,Evans J, SkeltonM, Castel S,Wiesner L, et al. 2015. An expanded analysis of pharmacogenetics determinants of efavirenz response that includes 3-UTR single nucleotide polymorphisms among black South African HIV/AIDS patients. Front. Genet. 6:356
114. Tishkoff SA, Varkonyi R, Cahinhinan N, Abbes S, Argyropoulos G, et al. 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293:455-62
115. Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, et al. 2011. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat. Genet. 43:887-92
116. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. CA Cancer J. Clin. 65:87-108
117. UNAIDS. 2018. Global HIV & AIDS statistics-2018 fact sheet. Fact Sheet, UNAIDS, Geneva. http:// www.unaids.org/en/resources/fact-sheet
118. UyBico SJ,Pavel S, GrossCP. 2007. Recruiting vulnerable populations into research: a systematic review of recruitment interventions. J. Gen. Intern.Med. 22:852-63
119. Vergara C, Parker MM, Franco L, Cho MH, Valencia-Duarte AV, et al. 2018. Genotype imputation performance of three reference panels using African ancestry individuals. Hum. Genet. 137:281-92
120. Visscher PM, Brown MA, McCarthy MI, Yang J. 2012. Five years of GWAS discovery. Am. J. Hum. Genet. 90:7-24
121. Voight BF, Kang HM, Ding J, Palmer CD, Sidore C, et al. 2012. TheMetabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.PLOS Genet. 8:e1002793
122. Wojcik GL, Fuchsberger C, Taliun D, Welch R, Martin AR, et al. 2018. Imputation-aware tag SNP selection to improve power for large-scale, multi-ethnic association studies. G3 8:3255-67
123. Wojcik GL, GraffM,Nishimura KK, Tao R,Haessler J, et al. 2019. Genetic analyses of diverse populations improves discovery for complex traits. Nature 570:514-18
124. Women's Health Init. Study Group. 1998. Design of the Women's Health Initiative clinical trial and observational study. Control. Clin. Trials 19:61-109
125. Zhang L,Buzkova P,Wassel CL, RomanMJ, North KE, et al. 2013. Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four US populations: the Population Architecture Using Genomics and Epidemiology (PAGE) study. Atherosclerosis 228:390-99
126. Zhang Y, Qi G, Park J-H, Chatterjee N. 2018. Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits. Nat. Genet. 50:1318-26
127. Zubair N, Graff M, Luis Ambite J, Bush WS, Kichaev G, et al. 2016. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci. Hum. Mol. Genet. 25:5500-12