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1. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

Author

Guillaume Lettre, Cameron D Palmer, Taylor Young, Kenechi G Ejebe, Hooman Allayee, Emelia J Benjamin, Franklyn Bennett, Donald W Bowden, Aravinda Chakravarti, Al Dreisbach, Deborah N Farlow, Aaron R Folsom, Myriam Fornage, Terrence Forrester, Ervin Fox, Christopher A Haiman, Jaana Hartiala, Tamara B Harris, Stanley L Hazen, Susan R Heckbert, Brian E Henderson, Joel N Hirschhorn, Brendan J Keating, Stephen B Kritchevsky, Emma Larkin, Mingyao Li, Megan E Rudock, Colin A McKenzie, James B Meigs, Yang A Meng, Tom H Mosley, Anne B Newman, Christopher H Newton-Cheh, Dina N Paltoo, George J Papanicolaou, Nick Patterson, Wendy S Post, Bruce M Psaty, Atif N Qasim, Liming Qu, Daniel J Rader, Susan Redline, Muredach P Reilly, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Yongmei Liu, Peter Shrader, David S Siscovick, W H Wilson Tang, Herman A Taylor, Russell P Tracy, Ramachandran S Vasan, Kevin M Waters, Rainford Wilks, James G Wilson, Richard R Fabsitz, Stacey B Gabriel, Sekar Kathiresan, and Eric Boerwinkle

Subjects
Genetics, QH426-470
Abstract

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

Published
2011
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2. The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women

Author

Franklyn Bennett, Rainford J. Wilks, Kennedy Cruickshank, Norma McFarlane-Anderson, Terrence Forrester, Sharon Howell, and Cavelle Newsome

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Jamaica, Genotype, Endocrinology, Diabetes and Metabolism, Population, Arginine, Body Mass Index, Endocrinology, Insulin resistance, Gene Frequency, Diabetes mellitus, Internal medicine, Receptors, Adrenergic, beta, Medicine, Humans, Obesity, education, Abdominal obesity, Alleles, Aged, education.field_of_study, business.industry, Tryptophan, nutritional and metabolic diseases, Middle Aged, medicine.disease, Amino Acid Substitution, Hyperglycemia, Mutation (genetic algorithm), Mutation, Regression Analysis, Female, medicine.symptom, business, Body mass index, Weight gain
Abstract

The Trp64Arg mutation of the β 3 -adrenergic receptor (β 3 -AR) has been linked to earlier onset of non—insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increased capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53%, and of the Arg allele, 10.5%. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2-hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2-hour blood glucose levels was predicted by β 3 -AR, gender, age, and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.

Published
1998

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