Evidence map›Paper›PMID 21850057›Full record

ArticleAmerican journal of hypertension2011

Variants on chromosome 6p22.3 associated with blood pressure in the HyperGEN study: follow-up of FBPP quantitative trait loci.

Jeannette Simino, Gang Shi, Donna Arnett, Ulrich Broeckel, Steven C Hunt, Dabeeru C Rao

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Article in American journal of hypertension, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

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9citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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  9. The Role of INDY in Metabolic Regulation.Computational and structural biotechnology journal · 2013
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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jeannette SiminoDivision of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, USA.
Gang Shi
Donna Arnett
Ulrich Broeckel
Steven C Hunt
Dabeeru C Rao

Funding

HYPERGEN: GENETICS OF LEFT VENTRICULAR HYPERTROPHYR01HL055673 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ARNETT, DONNA K · 1996 to 2016
$18.1M
The Family Blood Pressure Program (Program Data Center)U01HL054473 · NHLBI · WASHINGTON UNIVERSITY · PI RAO, DABEERU C · 2000 to 2008
$5.8M
Post-Doctoral Research Training in Genetic EpidemiologyT32HL091823 · NHLBI · WASHINGTON UNIVERSITY · PI RAO, DABEERU C · 2008 to 2017
$2.1M
EXPLORING A NEW DIRECTION TO GENE DISCOVERY FOR HYPERTENSION IN THE LARGE FBPPR21HL095054 · NHLBI · WASHINGTON UNIVERSITY · PI RAO, DABEERU C · 2009 to 2010
$303k
NHLBI NIH HHS R01 HL055673NHLBI NIH HHS R01 HL55673NHLBI NIH HHS R21 HL095054NHLBI NIH HHS T32 HL091823NHLBI NIH HHS U01 HL054473NHLBI NIH HHS U01 HL54473
6 · The paper itself

Abstract

backgroundA 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).

methodsEthnic-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.

resultsThree 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).

conclusionsSignificant 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.

Indexed as

Quantitative Trait LociBlack or African AmericanBlack PeopleBlood PressureChromosomes, Human, Pair 6Chromosomes, Human, Pair 8Genome-Wide Association StudyHumansHypertensionPolymorphism, Single NucleotideUnited StatesWhite People

Identifiers

PMID21850057
PMCPMC3406604

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