Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans
1 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2 Division of Endocrinology, Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, USA
3 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
4 Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI 53226, USA
5 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
BMC Medical Genetics 2012, 13:27 doi:10.1186/1471-2350-13-27Published: 11 April 2012
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.
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).
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.
This study highlights the importance of replication to confirm the validity of genome wide association study results.