TY - JOUR
T1 - Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans
T2 - The HyperGEN Study
AU - Arnett, Donna K.
AU - Li, Na
AU - Tang, Weihong
AU - Rao, Dabeeru C.
AU - Devereux, Richard B.
AU - Claas, Steven A.
AU - Kraemer, Rachel
AU - Broeckel, Ulrich
N1 - Funding Information:
This project was supported by NIH-NHLBI R01-555673 HyperGEN: Genetics of Left Ventricular Hypertrophy.
PY - 2009/5/19
Y1 - 2009/5/19
N2 - 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 inthe development of LV hypertrophy in humans.
AB - 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 inthe development of LV hypertrophy in humans.
UR - http://www.scopus.com/inward/record.url?scp=66649106445&partnerID=8YFLogxK
U2 - 10.1186/1471-2350-10-43
DO - 10.1186/1471-2350-10-43
M3 - Article
C2 - 19454037
AN - SCOPUS:66649106445
SN - 1471-2350
VL - 10
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 43
ER -