Background A recent meta-analysis of genome-wide linkage scans of blood pressure (BP) in the large (N = 13,044) Family Blood Pressure Program (FBPP) identified five quantitative trait loci (QTLs) on chromosomes 6, 8, 20, and 21. We conducted follow-up fine mapping studies in 1,251 African (AA) and 1,254 European American (EA) participants of the Hypertension Genetic Epidemiology Network (HyperGEN). Methods Ethnic-specific linear mixed effects models were used to test associations of BP with genotyped and imputed single nucleotide polymorphisms (SNPs) contained in the logarithm of odds (LOD) score ≥2 interval under each of the QTL peaks. We used multipoint variance components models to perform linkage analysis conditional on each significant SNP in the QTL region to see if the SNP explained the QTL. Results Three intergenic SNPs (rs898164, rs2876587, rs6935795) on chromosome 6p22.3 were significantly associated with pulse pressure (using appropriate Bonferroni correction). Conditioning on the significant SNPs reduced the chromosome 6 QTL linkage evidence by 14-30%. Both AAs and EAs exhibited suggestive associations between BP and intronic SNPs on chromosomes 8q24.12 (genes OPG in AAs, SAMD12 in EAs), 20q13.12 (genes SLC13A3 in AAs, SLC12A5 in EAs), and 21q21.1 (genes C21orf34 in AAs, BC039377 in EAs). Conclusions Significant associations with common SNPs explained less than 1/3 of the QTL evidence. Our results cannot refute the hypothesis that rare variants account for most of the statistical evidence for the FBPP linkage peaks. Whole genome resequencing can identify the variants driving the linkage peaks and genome-wide association study (GWAS) hits thereby spurring investigations to deepen our understanding of hypertension pathophysiology.
|Number of pages||7|
|Journal||American Journal of Hypertension|
|State||Published - Nov 2011|
Bibliographical noteFunding Information:
Supplementary material is linked to the online version of the paper at http:// www.nature.com/ajh Acknowledgments:We thank all HyperGEN participants.The following investigators are associated with the HyperGEN Network: S.C.H. (Network Director), Janet Hood, D.A., James S. Pankow, John H. Eckfeldt, R. Curtis Ellison, Richard H. Myers, C. Charles Gu, Gerardo Heiss, Kari North, Paul Hopkins, Aldi T. Kraja, Jean-Marc Lalouel, Mark Leppert, Albert Oberman, Cora E. Lewis, Michael A. Province, D.C.R.,Treva Rice, and RobertWeiss.This research was partly supported by Grants T32 HL091823, U01 HL54473, R21 HL095054, and R01 HL55673 from the National Heart, Lung, and Blood Institute.
- blood pressure
- fine mapping
ASJC Scopus subject areas
- Internal Medicine