title: Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors.
abstract: 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.
  
  
  
  We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Steffan D
authors.initials: SD
authors.lastname: Bos
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway/Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: 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.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Schork
authors.affiliation: 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.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.affiliation: 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.
authors.forename: Aree
authors.initials: A
authors.lastname: Witoelar
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA/Department of Radiology, University of California-San Diego, La Jolla, CA, USA.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.affiliation: 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.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, USA.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.affiliation: 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.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: 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.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D056426:Genetic Loci; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
keywords: Multiple sclerosis; cardiovascular risk factors; gene discovery; pleiotropy