Research article

Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

Donna K Arnett¹ , Na Li² , Weihong Tang³ , Dabeeru C Rao⁴ , Richard B Devereux⁵ , Steven A Claas¹ , Rachel Kraemer⁶ and Ulrich Broeckel⁶

¹Department of Epidemiology, School of Public Health, University of Alabama at Birmingham 1530 3rd Avenue South, Birmingham AL 35294-0022, USA

²Division of Biostatistics, University of Minnesota, A460 Mayo Building, 420 Delaware St SE, Minneapolis, MN 55455, USA

³Division of Epidemiology and Community Health, University of Minnesota, West Bank Office Building, 1300 S. Second Street, Suite 300, Minneapolis, MN 55454-1015, USA

⁴Division of Biostatistics, Washington University in St. Louis, 660 South Euclid Avenue, Box 8067, St Louis, MO 63110-1093, USA

⁵Division of Cardiology, Weill Medical College of Cornell University, Greenberg Division of Cardiology, 520 East 70th Street, 4th Floor, New York, NY 10021, USA

⁶Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA

author email corresponding author email

BMC Medical Genetics 2009, 10:43doi:10.1186/1471-2350-10-43

Published:	19 May 2009

Abstract

Background

We conducted a genome-wide association study (GWAS) and validation study for left ventricular (LV) mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101) and controls (N = 101) were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q < 0.8) single-nucleotide polymorphisms (SNPs) from the genome-wide study were successfully genotyped using quantitative real time PCR in a validation study.

Results

Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P ≤ 0.05) associated with LV mass after correction for multiple testing. One SNP (rs756529) is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population.

Conclusion

These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.