Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology

• Published in: Genes Vol. 12; no. 8; p. 1194
• Main Authors: Burt, Olivia, Johnston, Keira J A, Graham, Nicholas, Cullen, Breda, Lyall, Donald M, Lyall, Laura M, Pell, Jill P, Ward, Joey, Smith, Daniel J, Strawbridge, Rona J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.07.2021; MDPI
• Subjects: Antihypertensives; Biobanks; Bipolar disorder; Blood pressure; Blood Pressure - genetics; Body mass index; Cardiovascular Diseases - genetics; Gene expression; Genetic analysis; Genetic diversity; Genetic Pleiotropy; Genetic Variation; Genomes; Genotyping; Glycoproteins - genetics; Hedonic response; Humans; Hypertension; Linkage Disequilibrium; Medicin och hälsovetenskap; Mental Disorders - genetics; Metabolic Diseases - genetics; Nerve Tissue Proteins - genetics; Neurosis; Obesity; Pleiotropy; Population structure; Questionnaires; Stroke; Values; United Kingdom > UK; blood pressure; cardiovascular disease; psychiatric illness; anhedonia; neuroticism; central obesity; mood instability; ASTN2; metabolic disease; BMI
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12081194

The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of in relation to a wide range of relevant traits. Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent. Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through , however most of the other signals are likely acting through other genes in the locus. Our systematic analysis demonstrates that has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.