Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases

Oscar Franzén, Raili Ermel, Ariella Cohain, Nicholas K. Akers, Antonio Di Narzo, Husain A. Talukdar, Hassan Foroughi-Asl, Claudia Giambartolomei, John F. Fullard, Katyayani Sukhavasi, Sulev Köks, Li Ming Gan, Chiara Giannarelli, Jason C. Kovacic, Christer Betsholtz, Bojan Losic, Tom Michoel, Ke Hao, Panos Roussos, Josefin SkogsbergArno Ruusalepp, Eric E. Schadt, Johan L.M. Björkegren

Research output: Contribution to journalArticlepeer-review

174 Scopus citations


Genome-wide association studies (GWAS) have identified hundreds of cardiometabolic disease (CMD) risk loci. However, they contribute little to genetic variance, and most downstream gene-regulatory mechanisms are unknown.We genotyped and RNAsequenced vascular and metabolic tissues from 600 coronary artery disease patients in the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task study (STARNET). Gene expression traits associated with CMD risk single-nucleotide polymorphism (SNPs) identified by GWAS were more extensively found in STARNET than in tissue- and disease-unspecific gene-tissue expression studies, indicating sharing of downstream cis-/trans-gene regulation across tissues and CMDs. In contrast, the regulatory effects of other GWAS risk SNPs were tissue-specific; abdominal fat emerged as an important gene-regulatory site for blood lipids, such as for the low-density lipoprotein cholesterol and coronary artery disease risk gene PCSK9. STARNET provides insights into gene-regulatory mechanisms for CMD risk loci, facilitating their translation into opportunities for diagnosis, therapy, and prevention.

Original languageEnglish
Pages (from-to)827-830
Number of pages4
Issue number6301
StatePublished - 19 Aug 2016


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