Faculty Collaboration Database

Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans. BMC Med Genet 2012 Apr 11;13:27

Date

04/13/2012

Pubmed ID

22494468

Pubmed Central ID

PMC3349540

DOI

10.1186/1471-2350-13-27

Scopus ID

2-s2.0-84859506440 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

BACKGROUND: A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives.

METHODS: We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13) found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power) to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications).

RESULTS: For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204) showed borderline association (p = 0.006) with hypertension status using recessive model and systolic blood pressure (p = 0.02), but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002). In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant.

CONCLUSIONS: This study highlights the importance of replication to confirm the validity of genome wide association study results.

Author List

Kidambi S, Ghosh S, Kotchen JM, Grim CE, Krishnaswami S, Kaldunski ML, Cowley AW Jr, Patel SB, Kotchen TA

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Srividya Kidambi MD Sr Medical Director, Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Pressure
Cadherins
Case-Control Studies
Female
Fluorescent Dyes
Gene Frequency
Genome-Wide Association Study
Genotype
Humans
Hypertension
Male
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Regression Analysis