Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness
Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness
Abstract Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. While it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition towards loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we conducted a genome-wide association (GWAS) meta-analysis of loneliness (N=475,661), report 12 associated loci (two novel) and significant genetic correlations with 34 other complex traits. The polygenic basis for loneliness was significantly enriched for evolutionary constrained genes and genes expressed in specific brain tissues: (frontal) cortex, cerebellum, anterior cingulate cortex, and substantia nigra. We built polygenic scores based on this GWAS meta-analysis to explore the genetic association between loneliness and health outcomes in an independent sample of 18,498 individuals for whom electronic health records were available. A genetic predisposition towards loneliness predicted cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, effect of body fat on loneliness, and a similar weaker causal effect of BMI. Our results provide a framework for ongoing studies of the genetic basis of loneliness and its role in mental and physical health.
Neumann Alexander、Cacioppo Stephanie、Willemsen Gonneke、Mosing Miriam、Pedersen Nancy L.、Amin Najaf、Szilagyi Ingrid、Boomsma Dorret I.、Dennis Jessica、Fontanillas Pierre、Elson Sarah、The 23andme Research Team、der Zee Matthijs van、Baselmans Bart、Hottenga Jouke Jan、Abdellaoui Abdel、Cacioppo John T.、van Duijn Cornelia M、Sealock Julia、Tiemeier Henning、Sanchez-Roige Sandra、Yu Li、Davis Lea K.、Palmer Abraham A.、Treur Jorien L.、Verweij Karin、Nivard Michel、Fung Ip Hill
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical CenterCenter for Cognitive and Social Neuroscience, Department of Psychology, The University of ChicagoDepartment of Biological Psychology, Vrije UniversiteitDepartment of Neuroscience, Karolinska Institutet||Department of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetGenetic Epidemiology Unit, Department of EpidemiologyDepartment of Epidemiology, Erasmus Medical CenterDepartment of Biological Psychology, Vrije UniversiteitVanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University23andMe, Inc.23andMe, Inc.23andMe, Inc.Department of Biological Psychology, Vrije UniversiteitDepartment of Biological Psychology, Vrije UniversiteitDepartment of Biological Psychology, Vrije UniversiteitDepartment of Biological Psychology, Vrije Universiteit||Department Psychiatry, Amsterdam UMC, University of AmsterdamCenter for Cognitive and Social Neuroscience, Department of Psychology, The University of ChicagoGenetic Epidemiology Unit, Department of Epidemiology||Translational Epidemiology, Faculty Science, Leiden UniversityVanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt UniversityDepartment of Epidemiology, Erasmus Medical Center||Department of Psychiatry, Erasmus Medical CenterDepartment of Psychiatry, University of California San DiegoDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetVanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt UniversityDepartment of Psychiatry, University of California San DiegoDepartment Psychiatry, Amsterdam UMC, University of Amsterdam||School of Experimental Psychology, University of Bristol||MRC Integrative Epidemiology Unit, University of BristolDepartment Psychiatry, Amsterdam UMC, University of AmsterdamDepartment of Biological Psychology, Vrije UniversiteitDepartment of Biological Psychology, Vrije Universiteit
医药卫生理论医学研究方法神经病学、精神病学
Neumann Alexander,Cacioppo Stephanie,Willemsen Gonneke,Mosing Miriam,Pedersen Nancy L.,Amin Najaf,Szilagyi Ingrid,Boomsma Dorret I.,Dennis Jessica,Fontanillas Pierre,Elson Sarah,The 23andme Research Team,der Zee Matthijs van,Baselmans Bart,Hottenga Jouke Jan,Abdellaoui Abdel,Cacioppo John T.,van Duijn Cornelia M,Sealock Julia,Tiemeier Henning,Sanchez-Roige Sandra,Yu Li,Davis Lea K.,Palmer Abraham A.,Treur Jorien L.,Verweij Karin,Nivard Michel,Fung Ip Hill.Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness[EB/OL].(2025-03-28)[2025-08-19].https://www.biorxiv.org/content/10.1101/468835.点此复制
评论