Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors

Yunpeng Wang; Steffan D Bos; Hanne F Harbo; Wesley K Thompson; Andrew J Schork; Francesco Bettella; Aree Witoelar; Benedicte A Lie; Wen Li; Linda K McEvoy; Srdjan Djurovic; Rahul S Desikan; Anders M Dale; Ole A Andreassen

doi:10.1177/1352458516635873

Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors

Mult Scler. 2016 Dec;22(14):1783-1793. doi: 10.1177/1352458516635873. Epub 2016 Feb 26.

Authors

Affiliations

¹ NORMENT, K.G. Jebsen Psychosis Research Centre, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway/Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway/Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA/Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
² Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁴ Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA/Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA/Center for Human Development, University of California, San Diego, La Jolla, CA, USA.
⁵ NORMENT, K.G. Jebsen Psychosis Research Centre, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway/Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁶ Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
⁷ Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA/Department of Radiology, University of California-San Diego, La Jolla, CA, USA.
⁸ NORMENT, K.G. Jebsen Psychosis Research Centre, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway/Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway/Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
⁹ Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, USA.
¹⁰ NORMENT, K.G. Jebsen Psychosis Research Centre, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway/Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA/Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA/Department of Radiology, University of California, San Diego, La Jolla, CA, USA/Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA amdale@ucsd.edu.
¹¹ NORMENT, K.G. Jebsen Psychosis Research Centre, Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway/Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway/Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.

Abstract

Background: Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.

Objective: We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.

Methods: Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.

Results and conclusion: Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.

Keywords: Multiple sclerosis; cardiovascular risk factors; gene discovery; pleiotropy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases / blood
Cardiovascular Diseases / epidemiology
Cardiovascular Diseases / genetics*
Cardiovascular Diseases / physiopathology
Genetic Loci
Genetic Pleiotropy
Genome-Wide Association Study*
Humans
Multiple Sclerosis / genetics*
Polymorphism, Single Nucleotide
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding