@article {1316, title = {Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource (CARe) project.}, journal = {Circ Cardiovasc Genet}, volume = {4}, year = {2011}, month = {2011 Oct}, pages = {557-64}, abstract = {

BACKGROUND: The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.

METHODS AND RESULTS: We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95\% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95\% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95\% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95\% CI, 1.16-1.69; P=0.0005).

CONCLUSIONS: In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.

}, keywords = {African Americans, Aged, Alleles, Atrial Fibrillation, Chromosomes, Human, Pair 4, Cohort Studies, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Receptors, Interleukin-6, Risk Factors, Stroke, United States}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.110.959197}, author = {Schnabel, Renate B and Kerr, Kathleen F and Lubitz, Steven A and Alkylbekova, Ermeg L and Marcus, Gregory M and Sinner, Moritz F and Magnani, Jared W and Wolf, Philip A and Deo, Rajat and Lloyd-Jones, Donald M and Lunetta, Kathryn L and Mehra, Reena and Levy, Daniel and Fox, Ervin R and Arking, Dan E and Mosley, Thomas H and M{\"u}ller-Nurasyid, Martina and Young, Taylor R and Wichmann, H-Erich and Seshadri, Sudha and Farlow, Deborah N and Rotter, Jerome I and Soliman, Elsayed Z and Glazer, Nicole L and Wilson, James G and Breteler, Monique M B and Sotoodehnia, Nona and Newton-Cheh, Christopher and K{\"a}{\"a}b, Stefan and Ellinor, Patrick T and Alonso, Alvaro and Benjamin, Emelia J and Heckbert, Susan R} } @article {1620, title = {Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.}, journal = {J Clin Psychopharmacol}, volume = {33}, year = {2013}, month = {2013 Apr}, pages = {206-10}, chapter = {206}, abstract = {

Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 {\texttimes} 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 {\texttimes} 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 {\texttimes} 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.

}, keywords = {Aged, Alcohol Drinking, Alcoholism, Case-Control Studies, European Continental Ancestry Group, Feasibility Studies, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk}, issn = {1533-712X}, doi = {10.1097/JCP.0b013e318287009a}, author = {Hamidovic, Ajna and Goodloe, Robert J and Young, Taylor R and Styn, Mindi A and Mukamal, Kenneth J and Choquet, Helene and Kasberger, Jay L and Buxbaum, Sarah G and Papanicolaou, George J and White, Wendy and Volcik, Kelly and Spring, Bonnie and Hitsman, Brian and Levy, Daniel and Jorgenson, Eric} }