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

Mélanie Guirette, Jessie Lan, Nicola M. 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 J. 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 F. Tinker, Nora Franceschini, Tian Xiao 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: Contribution to journalArticlepeer-review


BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS: We analyzed up to 9420585 single nucleotide polymorphisms in up to 127282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35660) and UK Biobank (n=91622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at Pinteraction<5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (Pinteraction=4e-8; P for heterogeneity, 0.35) in European population, where the interaction effect size was 0.42±0.09 mmHg (Pinteraction=9.4e-7) and 0.20±0.06 mmHg (Pinteraction=0.001) in Cohorts for Heart and Aging Research in Genomic Epidemiology 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 variants (P=1e-300). Although the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by single nucleotide polymorphisms potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSIONS: We demonstrated gene-DASH diet score interaction effects on systolic BP in several loci. Studies with larger diverse populations are needed to validate our findings.

Original languageEnglish (US)
Pages (from-to)552-560
Number of pages9
Issue number3
StatePublished - Mar 1 2024


  • UK Biobank
  • blood pressure
  • cardiovascular diseases
  • gene-environment interaction
  • hypertension

ASJC Scopus subject areas

  • Internal Medicine

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