TY - JOUR
T1 - Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
AU - 23andMe Research Team
AU - Abdellaoui, Abdel
AU - Sanchez-Roige, Sandra
AU - Sealock, Julia
AU - Treur, Jorien L
AU - Dennis, Jessica
AU - Fontanillas, Pierre
AU - Elson, Sarah
AU - Nivard, Michel G
AU - Ip, Hill Fung
AU - van der Zee, Matthijs
AU - Baselmans, Bart M L
AU - Hottenga, Jouke Jan
AU - Willemsen, Gonneke
AU - Mosing, Miriam
AU - Lu, Yi
AU - Pedersen, Nancy L
AU - Denys, Damiaan
AU - Amin, Najaf
AU - M van Duijn, Cornelia
AU - Szilagyi, Ingrid
AU - Tiemeier, Henning
AU - Neumann, Alexander
AU - Verweij, Karin J H
AU - Cacioppo, Stephanie
AU - Cacioppo, John T
AU - Davis, Lea K
AU - Palmer, Abraham A
AU - Boomsma, Dorret I
N1 - © The Author(s) 2019. Published by Oxford University Press.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - 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 extended the genome-wide association study (GWAS) 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 electronic health record data to conduct a PheWAS with. A genetic predisposition towards loneliness was associated with cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, 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.
AB - 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 extended the genome-wide association study (GWAS) 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 electronic health record data to conduct a PheWAS with. A genetic predisposition towards loneliness was associated with cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, 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.
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UR - https://www.ncbi.nlm.nih.gov/pubmed/31518406
U2 - https://doi.org/10.1093/hmg/ddz219
DO - https://doi.org/10.1093/hmg/ddz219
M3 - Article
C2 - 31518406
SN - 0964-6906
VL - 28
SP - 3853
EP - 3865
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 22
ER -