Diversity and inclusion in genomic research: why the uneven progress?

Journal of Community Genetics - Tập 8 - Trang 255-266 - 2017
Amy R. Bentley1, Shawneequa Callier1,2, Charles N. Rotimi1
1Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, USA
2The George Washington University School of Medicine and Health Sciences, Washington, USA

Tóm tắt

Conducting genomic research in diverse populations has led to numerous advances in our understanding of human history, biology, and health disparities, in addition to discoveries of vital clinical significance. Conducting genomic research in diverse populations is also important in ensuring that the genomic revolution does not exacerbate health disparities by facilitating discoveries that will disproportionately benefit well-represented populations. Despite the general agreement on the need for genomic research in diverse populations in terms of equity and scientific progress, genomic research remains largely focused on populations of European descent. In this article, we describe the rationale for conducting genomic research in diverse populations by reviewing examples of advances facilitated by their inclusion. We also explore some of the factors that perpetuate the disproportionate attention on well-represented populations. Finally, we discuss ongoing efforts to ameliorate this continuing bias. Collaborative and intensive efforts at all levels of research, from the funding of studies to the publication of their findings, will be necessary to ensure that genomic research does not conserve historical inequalities or curtail the contribution that genomics could make to the health of all humanity.

Tài liệu tham khảo

Adeyemo AA et al (2015) Evaluation of genome wide association study associated type 2 diabetes susceptibility loci in sub Saharan Africans. Front Genet 6:335. doi:10.3389/fgene.2015.00335 Baker JL, Rotimi CN, Shriner D (2017) Human ancestry correlates with language and reveals that race is not an objective genomic classifier. Sci Rep 7:1572. doi:10.1038/s41598-017-01837-7 Band G et al (2013) Imputation-based meta-analysis of severe malaria in three African populations. PLoS Genet 9:e1003509. doi:10.1371/journal.pgen.1003509 Bentley AR, Rotimi CN (2012) Interethnic variation in lipid profiles: implications for underidentification of African-Americans at risk for metabolic disorders. Expert Rev Endocrinol Metab 7:659–667. doi:10.1586/eem.12.55 Bryc K, Durand Eric Y, Macpherson JM, Reich D, Mountain Joanna L (2015) The genetic ancestry of African Americans, Latinos, and European Americans across the United States. Am J Hum Genet 96:37–53. doi:10.1016/j.ajhg.2014.11.010 Burke W, Tarini B, Press NA, Evans JP (2011) Genetic screening. Epidemiol Rev 33:148–164. doi:10.1093/epirev/mxr008 Bustamante CD, De La Vega FM, Burchard EG (2011) Genomics for the world. Nature 475:163–165 Chimusa ER et al (2014) Genome-wide association study of ancestry-specific TB risk in the South African Coloured population. Hum Mol Genet 23:796–809. doi:10.1093/hmg/ddt462 Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37:161–165 Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354:1264–1272. doi:10.1056/NEJMoa054013 Cohn DV (2015) Census considers new approach to asking about race—by not using the term at all. http://www.pewresearch.org/fact-tank/2015/06/18/census-considers-new-approach-to-asking-about-race-by-not-using-the-term-at-all/. Accessed 13 Mar 2017 Collins FS, Varmus H (2015) A new initiative on precision medicine. N Engl J Med 372:793–795. doi:10.1056/NEJMp1500523 Cook MB et al (2014) A genome-wide association study of prostate cancer in West African men. Hum Genet 133:509–521. doi:10.1007/s00439-013-1387-z Cyranoski D (2012) Chinese genomics giant BGI plots commercial path. Nat Biotech 30:1159–1160. doi:10.1038/nbt1212-1159 Cyranoski D (2016) China embraces precision medicine on a massive scale. Nature 529:9–10. doi:10.1038/529009a de Vries J et al (2015) The H3Africa policy framework: negotiating fairness in genomics. Trends in genetics : TIG 31:117–119. doi:10.1016/j.tig.2014.11.004 Editors PM et al (2016) Towards equity in health: researchers take stock. PLoS Med 13:e1002186. doi:10.1371/journal.pmed.1002186 Fitzgerald K et al (2017) A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med 376:41–51. doi:10.1056/NEJMoa1609243 Freedman BI et al (2014) End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol 66:390–396. doi:10.1002/art.38220 Friedman DJ, Pollak MR (2011) Genetics of kidney failure and the evolving story of APOL1. J Clin Invest 121:3367–3374. doi:10.1172/JCI46263 Genomes Project C et al (2015) A global reference for human genetic variation. Nature 526:68–74. doi:10.1038/nature15393 Genovese G et al (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science:329, 841–845. doi:10.1126/science.1193032 Ginther DK, Schaffer WT, Schnell J, Masimore B, Liu F, Haak LL, Kington R (2011) Race, ethnicity, and NIH research awards. Science 333:1015–1019. doi:10.1126/science.1196783 Gouni-Berthold I, Descamps OS, Fraass U, Hartfield E, Allcott K, Dent R, März W (2016) Systematic review of published Phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia. Br J Clin Pharmacol 82:1412–1443. doi:10.1111/bcp.13066 Gurdasani D et al (2015) The African genome variation project shapes medical genetics in Africa. Nature 517:327–332. doi:10.1038/nature13997 Ha NT, Freytag S, Bickeboeller H (2014) Coverage and efficiency in current SNP chips. Eur J Hum Genet 22:1124–1130. doi:10.1038/ejhg.2013.304 Horton JD, Cohen JC, Hobbs HH (2007) Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem Sci 32:71–77. doi:10.1016/j.tibs.2006.12.008 Huang Q (2015) Genetic study of complex diseases in the post-GWAS era. J Genet Genomics 42:87–98. doi:10.1016/j.jgg.2015.02.001 Jallow M et al (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet 41:657–665. doi:10.1038/ng.388 Joubert BR, Lange EM, Franceschini N, Mwapasa V, North KE, Meshnick SR, Immunology NCfHAV (2010) A whole genome association study of mother-to-child transmission of HIV in Malawi. Genome Med 2:17. doi:10.1186/gm138 Julian BA, Gaston RS, Brown WM, Reeves-Daniel AM, Israni AK, Schladt DP, Pastan SO, Mohan S, Freedman BI, Divers J (2016) Effect of replacing race with apolipoprotein L1 genotype in calculation of kidney donor risk index. Am J Trans doi: 10.1111/ajt.14113 Kang SJ et al (2010) Genome-wide association of anthropometric traits in African- and African-derived populations. Hum Mol Genet 19:2725–2738. doi:10.1093/hmg/ddq154 Kasembeli AN et al (2015) APOL1 risk variants are strongly associated with HIV-associated nephropathy in black South Africans. J Am Soc Nephrol 26:2882–2890. doi:10.1681/ASN.2014050469 Kaye J, Heeney C, Hawkins N, de Vries J, Boddington P (2009) Data sharing in genomics—re-shaping scientific practice. Nat Rev Genet 10:331–335. doi:10.1038/nrg2573 Kim S et al (2016) Genetic influences on plasma homocysteine levels in African Americans and Yoruba Nigerians. J Alzheimers Dis 49:991–1003. doi:10.3233/JAD-150651 Knoppers BM (2014) Framework for responsible sharing of genomic and health-related data. HUGO J 8:3. doi:10.1186/s11568-014-0003-1 Kopp JB et al (2011) APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 22:2129–2137. doi:10.1681/ASN.2011040388 Ku E et al (2017) Strict blood pressure control associates with decreased mortality risk by APOL1 genotype. Kidney Int 91:443–450. doi:10.1016/j.kint.2016.09.033 Larson C (2013) Inside China’s genome factory. https://www.technologyreview.com/s/511051/inside-chinas-genome-factory/. Accessed 02/23/2017 Li MJ, Sham PC, Wang J (2012) Genetic variant representation, annotation and prioritization in the post-GWAS era. Cell Res 22:1505–1508. doi:10.1038/cr.2012.106 Lingappa JR et al (2011) Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One 6:e28632. doi:10.1371/journal.pone.0028632 Ma L et al (2016) APOL1 renal-risk variants induce mitochondrial dysfunction. J Am Soc Nephrol. doi:10.1681/asn.2016050567 Malaria Genomic Epidemiological N (2017) Ethics of collaboration https://www.malariagen.net/ethics/ethics-collaboration. Accessed March 10 2017 Malaria Genomic Epidemiology N, Band G, Rockett KA, Spencer CC, Kwiatkowski DP (2015) A novel locus of resistance to severe malaria in a region of ancient balancing selection. Nature 526:253–257. doi:10.1038/nature15390 Manrai AK et al (2016) Genetic misdiagnoses and the potential for health disparities. N Engl J Med 375:655–665. doi:10.1056/NEJMsa1507092 Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE (1995) Prevalence of hypertrophic cardiomyopathy in a general population of young adults Echocardiographic Analysis of 4111 Subjects in the CARDIA Study 92:785–789 doi: 10.1161/01.cir.92.4.785 Mathias RA et al (2016) A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome. Nat Commun 7:12522. doi:10.1038/ncomms12522 McDonald M, Townsend A, Cox SM, Paterson ND, Lafreniere D (2008) Trust in health research relationships: accounts of human subjects. J Empir Res Hum Res Ethics 3:35–47. doi:10.1525/jer.2008.3.4.35 Milet J, Sabbagh A, Migot-Nabias F, Luty AJ, Gaye O, Garcia A, Courtin D (2016) Genome-wide association study of antibody responses to Plasmodium falciparum candidate vaccine antigens. Genes Immun 17:110–117. doi:10.1038/gene.2015.59 Moore JX, Chaudhary N, Akinyemiju T (2017) Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis 14:E24. doi:10.5888/pcd14.160287 Movahed MR, Strootman D, Bates S, Sattur S (2010) Prevalence of suspected hypertrophic cardiomyopathy or left ventricular hypertrophy based on race and gender in teenagers using screening echocardiography. Cardiovasc Ultrasound 8:54. doi:10.1186/1476-7120-8-54 Mtatiro SN et al (2014) Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania. PLoS One 9:e111464. doi:10.1371/journal.pone.0111464 Mulder NJ et al (2016) H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa. Genome Res 26:271–277. doi:10.1101/gr.196295.115 N’Diaye A et al (2011) Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry. PLoS Genet 7:e1002298. doi:10.1371/journal.pgen.1002298 Need AC, Goldstein DB (2009) Next generation disparities in human genomics: concerns and remedies. Trends Genet 25:489–494. doi:10.1016/j.tig.2009.09.012 Ng MCY et al (2014) Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLOS Genetics 10:e1004517. doi:10.1371/journal.pgen.1004517 Nielsen R, Akey JM, Jakobsson M, Pritchard JK, Tishkoff S, Willerslev E (2017) Tracing the peopling of the world through genomics. Nature 541:302–310. doi:10.1038/nature21347 Oh SS et al (2015) Diversity in clinical and biomedical research: a promise yet to be fulfilled. PLoS Med 12:e1001918. doi:10.1371/journal.pmed.1001918 Oh SS, White MJ, Gignoux CR, Burchard EG (2016) Making precision medicine socially precise. Take a deep breath. Am J Respir Crit Care Med 193:348–350. doi:10.1164/rccm.201510-2045ED Panofsky A, Bliss C (2017) Ambiguity and scientific authority: population classification in genomic science. Am Soc Rev 82:59-87. doi:10.1177/0003122416685812 Parsa A et al (2013) APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 369:2183–2196. doi:10.1056/NEJMoa1310345 Peralta CA, Bibbins-Domingo K, Vittinghoff E, Lin F, Fornage M, Kopp JB, Winkler CA (2016) APOL1 genotype and race differences in incident albuminuria and renal function decline. J Am Soc Nephrol 27:887–893. doi:10.1681/asn.2015020124 Petrovski S et al (2011) Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS 25:513–518. doi:10.1097/QAD.0b013e328343817b Polychronakos C, Alriyami M (2015) Diabetes in the post-GWAS era. Nat Genet 47:1373–1374. doi:10.1038/ng.3453 Popejoy AB, Fullerton SM (2016) Genomics is failing on diversity. Nature 538:161–164. doi:10.1038/538161a Price AL, Spencer CCA, Donnelly P (2015) Progress and promise in understanding the genetic basis of common diseases. Proc Royal Soc B Biol Sci 282 doi: 10.1098/rspb.2015.1684 Ramsay M, Sankoh O, study amotA-G, Consortium tHA (2015) African partnerships through the H3Africa Consortium bring a genomic dimension to longitudinal population studies on the continent. Int J Epidemiol. doi:10.1093/ije/dyv187 Ramsuran V et al (2011) Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. Clin Infect Dis 52:1248–1256. doi:10.1093/cid/cir119 Ray KK et al. (2017) Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol N Engl J Med 376:1430-1440 doi:10.1056/NEJMoa1615758 Reeves-Daniel AM et al (2011) The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant 11:1025–1030. doi:10.1111/j.1600-6143.2011.03513.x Roth EM et al (2016) A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis 254:254–262. doi:10.1016/j.atherosclerosis.2016.08.043 Rotimi C et al (2007) Community engagement and informed consent in the International HapMap project Community. Genet 10:186–198. doi:10.1159/000101761 Rotimi C, Mulder N (2014) Data acquisition and data/knowledge sharing in global genomic studies. Appl Transl Genomics 3:109–110. doi:10.1016/j.atg.2014.09.002 Rotimi CN, Jorde LB (2010) Ancestry and disease in the age of genomic medicine. N Engl J Med 363:1551–1558. doi:10.1056/NEJMra0911564 Rotimi CN, Tekola-Ayele F, Baker JL, Shriner D (2016) The African diaspora: history, adaptation and health. Curr Opin Genet Dev 41:77–84. doi:10.1016/j.gde.2016.08.005 Russell GW (2016) China plans leading role in ‘precision medicine’ field. The University of Hong Kong. http://jmsc.hku.hk/reportinghealth2016/2016/04/06/china-plans-leading-role-in-precision-medicine-field/. Accessed 02/23/2017 2017 Sabatine MS et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. doi:10.1056/NEJMoa1615664 Satcher D, Fryer GE Jr, McCann J, Troutman A, Woolf SH, Rust G (2005) What if we were equal? A comparison of the black-white mortality gap in 1960 and 2000. Health Aff (Millwood) 24:459–464. doi:10.1377/hlthaff.24.2.459 Science and inequality (2016) Nature 537:465. doi:10.1038/537465a Scott LJ et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345. doi:10.1126/science.1142382 Sheridan C (2013) Phase 3 data for PCSK9 inhibitor wows. Nat Biotech 31:1057–1058. doi:10.1038/nbt1213-1057 Shriner D, Adeyemo A, Rotimi CN (2011) Joint ancestry and association testing in admixed individuals. PLoS Comput Biol 7:e1002325. doi:10.1371/journal.pcbi.1002325 Shriner D, Tekola-Ayele F, Adeyemo A, Rotimi CN (2014) Genome-wide genotype and sequence-based reconstruction of the 140,000 year history of modern human ancestry. Sci Rep 4:6055. doi:10.1038/srep06055 Skloot R (2011) The immortal life of Henrietta Lacks, 1st edn. Broadway Paperbacks, New York Sladek R et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885. doi:10.1038/nature05616 Tarver-Carr ME, Powe NR, Eberhardt MS, LaVeist TA, Kington RS, Coresh J, Brancati FL (2002) Excess risk of chronic kidney disease among African-American versus white subjects in the United States: a population-based study of potential explanatory factors. J Am Soc Nephrol 13:2363–2370 Tekola-Ayele F et al (2015a) Novel genomic signals of recent selection in an Ethiopian population. Eur J Hum Genet 23:1085–1092. doi:10.1038/ejhg.2014.233 Tekola-Ayele F et al (2015b) Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome. Mol Gen Metab 116:305–313. doi:10.1016/j.ymgme.2015.10.008 Tekola Ayele F et al (2012) HLA class II locus and susceptibility to podoconiosis. N Engl J Med 366:1200–1208. doi:10.1056/NEJMoa1108448 The H3Africa Consortium (2014) Enabling the genomic revolution in Africa: H3Africa is developing capacity for health-related genomics research in Africa. Science (N Y NY) 344:1346–1348. doi:10.1126/science.1251546 Thomson R et al (2014) Evolution of the primate trypanolytic factor APOL1. Proc Natl Acad Sci U S A 111:E2130–E2139. doi:10.1073/pnas.1400699111 Thye T et al (2012) Common variants at 11p13 are associated with susceptibility to tuberculosis. Nat Genet 44:257–259. doi:10.1038/ng.1080 Thye T et al. (2010) Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2 Nat Genet 42:739-741 doi:10.1038/ng.639 Tindana P et al (2015) Community engagement strategies for genomic studies in Africa: a review of the literature. BMC Med Ethics 16:24. doi:10.1186/s12910-015-0014-z Trinidad SB, Fullerton SM, Bares JM, Jarvik GP, Larson EB, Burke W (2010) Genomic research and wide data sharing: views of prospective participants. Genet Med 12:486–495. doi:10.1097/GIM.0b013e3181e38f9e Wells JC (2012) Ethnic variability in adiposity, thrifty phenotypes and cardiometabolic risk: addressing the full range of ethnicity, including those of mixed ethnicity. Obes Rev 13(Suppl 2):14–29. doi:10.1111/j.1467-789X.2012.01034.x Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L, Parkinson, H (2013) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42(D1):D1001–D1006. doi:10.1093/nar/gkt1229 Yarborough M, Fryer-Edwards K, Geller G, Sharp RR (2009) Transforming the culture of biomedical research from compliance to trustworthiness: insights from nonmedical sectors. Acad Med 84:472–477. doi:10.1097/ACM.0b013e31819a8aa6 Zhang Y, Li Q, Wang X, Zhou X (2015) China biobanking. In: Karimi-Busheri F (ed) Biobanking in the 21st century. Springer International Publishing, Cham, pp 125–140. doi:10.1007/978-3-319-20579-3_10 Zhao X, Wang P, Tao X, Zhong N (2013) Genetic services and testing in China. J Commun Genet 4:379–390. doi:10.1007/s12687-013-0144-2