Skip to main content
Journal cover image

DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation.

Publication ,  Journal Article
Richard, MA; Huan, T; Ligthart, S; Gondalia, R; Jhun, MA; Brody, JA; Irvin, MR; Marioni, R; Shen, J; Tsai, P-C; Montasser, ME; Jia, Y; Liu, C ...
Published in: Am J Hum Genet
December 7, 2017

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p < 1.6 × 10-3). The replicated methylation sites are heritable (h2 > 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

December 7, 2017

Volume

101

Issue

6

Start / End Page

888 / 902

Location

United States

Related Subject Headings

  • Tetraspanins
  • Quantitative Trait Loci
  • Nerve Tissue Proteins
  • Middle Aged
  • Mendelian Randomization Analysis
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Variation
  • Epigenesis, Genetic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Richard, M. A., Huan, T., Ligthart, S., Gondalia, R., Jhun, M. A., Brody, J. A., … Fornage, M. (2017). DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation. Am J Hum Genet, 101(6), 888–902. https://doi.org/10.1016/j.ajhg.2017.09.028
Richard, Melissa A., Tianxiao Huan, Symen Ligthart, Rahul Gondalia, Min A. Jhun, Jennifer A. Brody, Marguerite R. Irvin, et al. “DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation.Am J Hum Genet 101, no. 6 (December 7, 2017): 888–902. https://doi.org/10.1016/j.ajhg.2017.09.028.
Richard MA, Huan T, Ligthart S, Gondalia R, Jhun MA, Brody JA, et al. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation. Am J Hum Genet. 2017 Dec 7;101(6):888–902.
Richard, Melissa A., et al. “DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation.Am J Hum Genet, vol. 101, no. 6, Dec. 2017, pp. 888–902. Pubmed, doi:10.1016/j.ajhg.2017.09.028.
Richard MA, Huan T, Ligthart S, Gondalia R, Jhun MA, Brody JA, Irvin MR, Marioni R, Shen J, Tsai P-C, Montasser ME, Jia Y, Syme C, Salfati EL, Boerwinkle E, Guan W, Mosley TH, Bressler J, Morrison AC, Liu C, Mendelson MM, Uitterlinden AG, van Meurs JB, BIOS Consortium, Franco OH, Zhang G, Li Y, Stewart JD, Bis JC, Psaty BM, Chen Y-DI, Kardia SLR, Zhao W, Turner ST, Absher D, Aslibekyan S, Starr JM, McRae AF, Hou L, Just AC, Schwartz JD, Vokonas PS, Menni C, Spector TD, Shuldiner A, Damcott CM, Rotter JI, Palmas W, Liu Y, Paus T, Horvath S, O’Connell JR, Guo X, Pausova Z, Assimes TL, Sotoodehnia N, Smith JA, Arnett DK, Deary IJ, Baccarelli AA, Bell JT, Whitsel E, Dehghan A, Levy D, Fornage M. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation. Am J Hum Genet. 2017 Dec 7;101(6):888–902.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

December 7, 2017

Volume

101

Issue

6

Start / End Page

888 / 902

Location

United States

Related Subject Headings

  • Tetraspanins
  • Quantitative Trait Loci
  • Nerve Tissue Proteins
  • Middle Aged
  • Mendelian Randomization Analysis
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Variation
  • Epigenesis, Genetic