Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (M.G., J.L., J.M.).
Programs of Nutrition, Department of Health Sciences, Sargent College of Health & Rehabilitation Sciences, Boston University, MA (N.M.M.).
Hypertension. 2024 Mar;81(3):552-560. doi: 10.1161/HYPERTENSIONAHA.123.22334. Epub 2024 Jan 16.
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.
We analyzed up to 9 420 585 single nucleotide polymorphisms in up to 127 282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35 660) and UK Biobank (n=91 622) and performed European population-specific and cross-population meta-analyses.
We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at <5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (=4e-8; for heterogeneity, 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (=9.4e-7) and 0.20±0.06 mm Hg (=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 (=4e-273) and cis-DNA methylation quantitative trait loci variants (=1e-300). Although the closest gene for rs117878928 is , the highest narrow sense heritability accounted by single nucleotide polymorphisms potentially interacting with the DASH diet score in this locus was for gene at 15q25.1.
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.
多吃蔬菜水果、减少钠摄入的得舒饮食(DASH)可降低血压(BP)。我们检测了基因型与 DASH 饮食评分在收缩压方面的相互作用。
我们分析了来自于 6 个人群群组(91%为欧洲人群)的 127282 个人,共计 9420585 个单核苷酸多态性(SNP),其中包括来自于心血管与衰老研究中的基因组流行病学合作研究队列(n=35660)和英国生物库(n=91622)。我们进行了欧洲人群特异性和跨人群荟萃分析。
在欧洲人群特异性分析中,我们鉴定出 3 个位于 15q25.1 的基因座,在跨人群分析中鉴定出另外 4 个基因座,均达到了<5e-8 的显著性阈值。我们观察到 rs117878928 位于 15q25.1(次要等位基因频率,0.03)与 DASH 饮食评分(=4e-8;异质性检验,0.35)之间存在一致的交互作用,在心血管与衰老研究中的基因组流行病学合作研究队列和英国生物库中的交互作用效应大小分别为 0.42±0.09mm Hg(=9.4e-7)和 0.20±0.06mm Hg(=0.001)。rs117878928 周围 1Mb 区域富集了 cis-表达数量性状基因座(eQTL)变体(=4e-273)和 cis-DNA 甲基化数量性状基因座变体(=1e-300)。尽管 rs117878928 最近的基因是 ,但在这个基因座中,与 DASH 饮食评分相互作用的单核苷酸多态性可能对基因 具有最高的窄义遗传力。
我们在多个基因座上证明了基因-DASH 饮食评分相互作用对收缩压的影响。需要更大、更多样化的人群研究来验证我们的发现。