Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
Year: 2019
Type: article
Study design: Observational Study
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. Although 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. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddz219
Authors: Abdel Abdellaoui, Sandra Sanchez-Roige, Julia Sealock, Jorien L Treur, Jessica Dennis, Pierre Fontanillas, Sarah Elson, Michel G Nivard, Hill Fung Ip, Matthijs van der Zee, Bart M L Baselmans, Jouke Jan Hottenga, Gonneke Willemsen, Miriam Mosing, Yi Lu, Nancy L Pedersen, Damiaan Denys, Najaf Amin, Cornelia M van Duijn, Ingrid Szilagyi, Henning Tiemeier, Alexander Neumann, Karin J H Verweij, Stephanie Cacioppo, John T Cacioppo, Lea K Davis, Abraham A Palmer, Dorret I Boomsma
Institutions: Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, University of Amsterdam, University of California San Diego, Vanderbilt University, University of Bristol, MRC Integrative Epidemiology Unit, 23andMe (United States), Karolinska Institutet, Erasmus MC, Leiden University, University of Chicago
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: Tobacco-Related Disease Research Program, Vanderbilt University, Vanderbilt-Ingram Cancer Center, National Alliance for Research on Schizophrenia and Depression, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Avera Institute for Human Genetics, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1028663679, G1201814862, G1303670329, G1409398652, Pharmacogenomics of Arrhythmia Therapy, G1550360770, G178382592, G1845105935, G2103760183, G2238725043, G2324588096, G2748385693, G2748465565, G2998239322, BBMRI-NL2.0: The NL-Biobank Research Facility, G3121967442, G3269002440, G3272792225, Improving Prediction of Drug Action, G357049385, G364208108, G3963195955, Genomics of Developmental Trajectories in Twins, G4049315607, Automated Storage and Retrieval of Biological Systems, Are there causal effects between tobacco and cannabis use and mental health disorders? A Mendelian randomization study, G483456127, G53215581, G5526428480, G5679716143, G5767309141, G6119330051, G6144234142, G6663973959, G6922361213, G70080636, Training Program on Genetic Variation and Human Phenotypes, G7220527126, Netherlands Twin Registry Repository: researching the interplay between genome and environment, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G7924559645, Discovering Biology for Neuropsychiatric Diseases Through Omics Studies on Comorbidities, Integration of Genomics & Transcriptomics in Normal Twins & Major Depression, Social Regulation of Gene Expression, G84497985, G8662178672, G86865590, G8953775245, G9000060478, G9000089795, G9000213099, Interdisciplinary Research Fellowship in NeuroAIDS, Cancer Center Support Grant, Core Grant in Vision Research, G961365294
OpenAlex ID: W2972698755