Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure
Author:
Guirette MélanieORCID, Lan Jessie, Mckeown Nicola, Brown Michael RORCID, Chen HanORCID, De Vries Paul SORCID, Kim Hyunju, Rebholz Casey MORCID, Morrison Alanna CORCID, Bartz Traci MORCID, Fretts Amanda MORCID, Guo XiuqingORCID, Lemaitre Rozenn N.ORCID, Liu Ching-TiORCID, Noordam RaymondORCID, de Mutsert Renée, Rosendaal Frits RORCID, Wang Carol AORCID, Beilin LawrenceORCID, Mori Trevor AORCID, Oddy Wendy H, Pennell Craig EORCID, Chai Jin Fang, Whitton Clare, van Dam Rob MORCID, Liu Jianjun, Tai E Shyong, Sim Xueling, Neuhouser Marian L, Kooperberg Charles, Tinker Lesley, Franceschini NoraORCID, Huan TianXiao, Winkler Thomas W, Bentley Amy R, Gauderman W. JamesORCID, Heerkens LucORCID, Tanaka Toshiko, Van Rooij Jeroen, Munroe Patricia BORCID, Warren Helen RORCID, Voortman TrudyORCID, Chen Honglei, Rao D.C., Levy DanielORCID, Ma JiantaoORCID
Abstract
AbstractObjectiveWe examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).MethodsWe analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.ResultsWe identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched withcis-expression quantitative trait loci (eQTL) variants (P = 4e-273) andcis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 isMTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for geneST20at 15q25.1.ConclusionWe demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.
Publisher
Cold Spring Harbor Laboratory
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