title: Identifying common genetic variants in blood pressure due to polygenic pleiotropy with associated phenotypes.
abstract: Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP.
authors.affiliation: Department of Radiology, University of California, San Diego, 8950 Villa La Jolla Dr, Suite C101, La Jolla, CA 92037-0841. amdale@ucsd.edu; and Ole A. Andreassen, NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, 0424 Oslo, Norway. Email o.a.andreassen@medisin.uio.no.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Sjur
authors.initials: S
authors.lastname: Reppe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Schork
authors.forename: Verena
authors.initials: V
authors.lastname: Zuber
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: Kaare
authors.initials: K
authors.lastname: Gautvik
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D002446:Celiac Disease / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D058685:Genetic Pleiotropy / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D006973:Hypertension / Q000235:genetics*; D020412:Multifactorial Inheritance / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics
keywords: arterial pressure; comorbidity; genetic pleiotropy; genome-wide association study