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


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 RNA-sequenced 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)827-30
Number of pages4
Issue number6301
Early online date19 Aug 2016
Publication statusE-pub ahead of print - 19 Aug 2016


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