title: Genetics of Type 2 Diabetes in U.S. Hispanic/Latino Individuals: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
abstract: Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2andKCNQ1)reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal atKCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 1.49 [95% CI 1.27-1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele atKCNQ1for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of U.S. Hispanics/Latinos.
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY qibin.qi@einstein.yu.edu.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Stilp
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Bertha
authors.initials: B
authors.lastname: Hidalgo
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Szpiro
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Genomics and Personalized Medicine Research and Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Maggie C Y
authors.initials: MCY
authors.lastname: Ng
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, and Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, and Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA.
authors.forename: Yii-Der Ida
authors.initials: YI
authors.lastname: Chen
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, and Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: M Larissa
authors.initials: ML
authors.lastname: Aviles-Santa
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: George
authors.initials: G
authors.lastname: Papanicolaou
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Department of Psychology, University of Miami, Miami, FL.
authors.forename: Neil
authors.initials: N
authors.lastname: Schneiderman
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, and Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014481:United States; D055815:Young Adult
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein