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<jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We conducted a genome-wide association study (GWAS) of HbA1c in 9,636 U.S. Hispanics\/Latinos without diabetes from the Hispanic Community Health Study\/Study of Latinos, followed by a replication among 4,729 U.S. Hispanics\/Latinos from three independent studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Our GWAS and replication analyses showed 10 previously known and novel loci associated with HbA1c at genome-wide significance levels (P &amp;lt; 5.0 \u00d7 10\u22128). In particular, two African ancestry\u2013specific variants, HBB-rs334 and G6PD-rs1050828, which are causal mutations for sickle cell disease and G6PD deficiency, respectively, had \u223c10 times larger effect sizes on HbA1c levels (\u03b2 = \u22120.31% [\u22123.4 mmol\/mol]) and \u22120.35% [\u22123.8 mmol\/mol] per minor allele, respectively) compared with other HbA1c-associated variants (0.03\u20130.04% [0.3\u20130.4 mmol\/mol] per allele). A novel Amerindian ancestry\u2013specific variant, HBM-rs145546625, was associated with HbA1c and hematologic traits but not with fasting glucose. The prevalence of hyperglycemia (prediabetes and diabetes) defined using fasting glucose or oral glucose tolerance test 2-h glucose was similar between carriers of HBB-rs334 or G6PD-rs1050828 HbA1c-lowering alleles and noncarriers, whereas the prevalence of hyperglycemia defined using HbA1c was significantly lower in carriers than in noncarriers (12.2% vs. 28.4%, P &amp;lt; 0.001). After recalibration of the HbA1c level taking HBB-rs334 and G6PD-rs1050828 into account, the prevalence of hyperglycemia in carriers was similar to noncarriers (31.3% vs. 28.4%, P = 0.28).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study in U.S. Hispanics\/Latinos found several ancestry-specific alleles associated with HbA1c through erythrocyte-related rather than glycemic-related pathways. The potential influences of these nonglycemic-related variants need to be considered when the HbA1c test is performed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc19-0168","type":"journal-article","created":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T19:59:07Z","timestamp":1560887947000},"page":"1784-1791","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["A Genome-Wide Association Study Identifies Blood Disorder\u2013Related Variants Influencing Hemoglobin A1c With Implications for Glycemic Status in U.S. Hispanics\/Latinos"],"prefix":"10.2337","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9218-8335","authenticated-orcid":false,"given":"Jee-Young","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tin L.","family":"Louie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Sofer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington, Seattle, WA"},{"name":"Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schurmann","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Below","sequence":"additional","affiliation":[{"name":"Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Qiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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