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<p>Coronary microvascular disease (CMVD) contributes to the large burden of ischemic heart disease (IHD), and there is a need for mechanistic insight and targeted therapies. Perfusion cardiac PET allows for the quantitative assessment of coronary flow reserve (CFR), which reflects coronary microvascular function. Here we use cardiac PET CFR as a measure of CMVD to perform first a gene association study with previously reported IHD loci and, second, an exploratory genome-wide association study. Of 241 known IHD loci, we identify 45 and 18 loci that are associated with CFR in populations genetically similar to African and European populations, respectively. We then perform a genome-wide association study followed by downstream and pathway analyses and identified an association between loci associated with CFR and the NF-κB pathway. We support these associations with targeted proteomic data. Our multi-omic analyses identified potential CMVD loci and suggest a role for the NF-κB pathway in CMVD.</p>

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Genome-wide association study of coronary flow reserve assessed by cardiac perfusion PET suggests a role for NF-κB pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Rasika Venkatesh,
  • Tess Cherlin,
  • Nicole Wayne,
  • Rachit Kumar,
  • Lindsay Guare,
  • Venkata P. Singamneni,
  • Brett Irving,
  • Scott Dudek,
  • Michael G. Levin,
  • Shefali Setia-Verma,
  • Marie A. Guerraty

摘要

Coronary microvascular disease (CMVD) contributes to the large burden of ischemic heart disease (IHD), and there is a need for mechanistic insight and targeted therapies. Perfusion cardiac PET allows for the quantitative assessment of coronary flow reserve (CFR), which reflects coronary microvascular function. Here we use cardiac PET CFR as a measure of CMVD to perform first a gene association study with previously reported IHD loci and, second, an exploratory genome-wide association study. Of 241 known IHD loci, we identify 45 and 18 loci that are associated with CFR in populations genetically similar to African and European populations, respectively. We then perform a genome-wide association study followed by downstream and pathway analyses and identified an association between loci associated with CFR and the NF-κB pathway. We support these associations with targeted proteomic data. Our multi-omic analyses identified potential CMVD loci and suggest a role for the NF-κB pathway in CMVD.