Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC).

Pubmed ID: 26162070

Pubmed Central ID: PMC4498745

Journal: PloS one

Publication Date: July 10, 2015

Affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States of America.

MeSH Terms: Humans, Male, Female, Gene Frequency, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Inheritance Patterns, Blood Pressure, Systole, Diastole, Genome, Human, Molecular Sequence Annotation, Black People, White People

Grants: HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, U01 HG004402, R01 HL059367, UL1RR025005, R01HL59367, UL1 RR025005, R01 HL086694, HHSN268200625226C, U01HG004402, R01HL087641, R01 HL087641, R01HL086694, HL086694, HHSN268201100009I, HHSN268201100005G, HHSN268201100008I, HHSN268201100011I, HHSN268201100005I, HHSN268201100007I

Authors: Boerwinkle E, Morrison AC, Salfati E, Chakravarti A

Cite As: Salfati E, Morrison AC, Boerwinkle E, Chakravarti A. Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC). PLoS One 2015 Jul 10;10(7):e0133031. doi: 10.1371/journal.pone.0133031. eCollection 2015.

Studies:

Abstract

Blood pressure (BP) is a heritable trait with multiple environmental and genetic contributions, with current heritability estimates from twin and family studies being ~ 40%. Here, we use genome-wide polymorphism data from the Atherosclerosis Risk in Communities (ARIC) study to estimate BP heritability from genomic relatedness among cohort members. We utilized data on 6,365,596 and 9,578,528 genotyped and imputed common single nucleotide polymorphisms (SNPs), in 8,901 European ancestry (EA) and 2,860 African Ancestry (AA) ARIC participants, respectively, and a mixed linear model for analyses, to make four observations. First, for BP measurements, the heritability is ~20%/~50% and ~27%/~39% for systolic (SBP)/diastolic (DBP) blood pressure in European and African ancestry individuals, respectively, consistent with prior studies. Second, common variants with allele frequency >10% recapitulate most of the BP heritability in these data. Third, the vast majority of BP heritability varies by chromosome, depending on its length, and is largely concentrated in noncoding genomic regions annotated as DNaseI hypersensitive sites (DHSs). Fourth, the majority of this heritability arises from loci not harboring currently known cardiovascular and renal genes. Recent meta-analyses of large-scale genome-wide association studies (GWASs) and admixture mapping have identified ~50 loci associated with BP and hypertension (HTN), and yet they account for only a small fraction (~2%) of the heritability.