Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

Mélanie Guirette, Jessie Lan, Nicola McKeown, Michael R Brown, Han Chen, Paul S DE Vries, Hyunju Kim, Casey M Rebholz, Alanna C Morrison, Traci M Bartz, Amanda M Fretts, Xiuqing Guo, Rozenn N Lemaitre, Ching-Ti Liu, Raymond Noordam, Renée DE Mutsert, Frits R Rosendaal, Carol A Wang, Lawrence Beilin, Trevor A MoriWendy H Oddy, Craig E Pennell, Jin Fang Chai, Clare Whitton, Rob M VAN Dam, Jianjun Liu, E Shyong Tai, Xueling Sim, Marian L Neuhouser, Charles Kooperberg, Lesley Tinker, Nora Franceschini, Tianxiao Huan, Thomas W Winkler, Amy R Bentley, W James Gauderman, Luc Heerkens, Toshiko Tanaka, Jeroen van Rooij, Patricia B Munroe, Helen R Warren, Trudy Voortman, Honglei Chen, D C Rao, Daniel Levy, Jiantao Ma

Research output: Working paperPreprintAcademic

5 Downloads (Pure)

Abstract

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).

METHODS: We 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.

RESULTS: We 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 with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1.

CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.

Original languageEnglish
DOIs
Publication statusPublished - 12 Nov 2023

Publication series

SeriesmedRxiv : the preprint server for health sciences

Fingerprint

Dive into the research topics of 'Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure'. Together they form a unique fingerprint.

Cite this