Jacqueline C. M. Witteman

Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25

Background— Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. Methods and Results— Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2×10−20) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. Conclusions— We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF.

Relation of Moderate Alcohol Consumption and Risk of Systemic Hypertension in Women

The relation between alcohol consumption and the risk of development of hypertension was studied among 58,218 US female registered nurses aged 39 to 59 years who were free of diagnosed systemic hypertension and other major diseases. In 1980, all of these women completed an independently validated dietary questionnaire, which included use of alcoholic beverages. During 4 years of follow-up, 3,275 women reported an initial diagnosis of hypertension; validity of the self-report measure was demonstrated in a subsample. When compared to nondrinkers, women drinking 20 to 34 g of alcohol per day (about 2 or 3 drinks) had a significantly elevated relative risk of 1.4; the 95% confidence interval (CI) was 1.2 to 1.7 after adjustment for age and Quetelets index. For women consuming greater than 35 g/day, the relative risk was 1.9 (95% CI 1.6 to 2.2). Adjustment for smoking and dietary variables did not alter these results. Independent significant associations were observed for the consumption of beer, wine and liquor. These prospective data suggest that alcohol intake of up to about 20 g/day does not increase the risk of hypertension among women, but beyond this level, the risk increases progressively.