Document Detail


Variants on chromosome 6p22.3 associated with blood pressure in the HyperGEN study: follow-up of FBPP quantitative trait loci.
MedLine Citation:
PMID:  21850057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jeannette Simino; Gang Shi; Donna Arnett; Ulrich Broeckel; Steven C Hunt; Dabeeru C Rao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-08-18
Journal Detail:
Title:  American journal of hypertension     Volume:  24     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-19     Completed Date:  2012-02-13     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1227-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
African Continental Ancestry Group / genetics*
Blood Pressure / genetics*
Chromosomes, Human, Pair 6 / genetics*
Chromosomes, Human, Pair 8 / genetics
European Continental Ancestry Group / genetics*
Genome-Wide Association Study
Humans
Hypertension / ethnology,  genetics*
Polymorphism, Single Nucleotide
Quantitative Trait Loci*
United States / epidemiology
Grant Support
ID/Acronym/Agency:
R01 HL055673/HL/NHLBI NIH HHS; R01 HL055673-15/HL/NHLBI NIH HHS; R01 HL55673/HL/NHLBI NIH HHS; R21 HL095054/HL/NHLBI NIH HHS; R21 HL095054/HL/NHLBI NIH HHS; R21 HL095054-02/HL/NHLBI NIH HHS; T32 HL091823/HL/NHLBI NIH HHS; T32 HL091823/HL/NHLBI NIH HHS; T32 HL091823-03/HL/NHLBI NIH HHS; U01 HL054473/HL/NHLBI NIH HHS; U01 HL054473-13/HL/NHLBI NIH HHS; U01 HL54473/HL/NHLBI NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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