Predicting loneliness with polygenic scores of social, psychological and psychiatric traits

Loneliness is a heritable trait that accompanies multiple disorders. The association between loneliness and mental health indices may partly be due to inherited biological factors. We constructed polygenic scores for 27 traits related to behavior, cognition and mental health and tested their prediction for self‐reported loneliness in a population‐based sample of 8798 Dutch individuals. Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar disorder were significantly associated with loneliness. Of the Big Five personality dimensions, polygenic scores for neuroticism and conscientiousness also significantly predicted loneliness, as did the polygenic scores for subjective well‐being, tiredness and self‐rated health. When including all polygenic scores simultaneously into one model, only 2 major depression polygenic scores remained as significant predictors of loneliness. When controlling only for these 2 MDD polygenic scores, only neuroticism and schizophrenia remain significant. The total variation explained by all polygenic scores collectively was 1.7%. The association between the propensity to feel lonely and the susceptibility to psychiatric disorders thus pointed to a shared genetic etiology. The predictive power of polygenic scores will increase as the power of the genome‐wide association studies on which they are based increases and may lead to clinically useful polygenic scores that can inform on the genetic predisposition to loneliness and mental health.

[1]  J. Cacioppo,et al.  Associations between loneliness and personality are mostly driven by a genetic association with Neuroticism. , 2018, Journal of personality.

[2]  Warren W. Kretzschmar,et al.  Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression , 2017, Nature Genetics.

[3]  John P. Rice,et al.  Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium , 2017, Biological Psychiatry.

[4]  W. G. Hill,et al.  Genetic contributions to self-reported tiredness , 2016, Molecular Psychiatry.

[5]  W. G. Hill,et al.  Genetic contributions to self-reported tiredness , 2016, Molecular Psychiatry.

[6]  Karl J. Friston,et al.  The Depressed Brain: An Evolutionary Systems Theory , 2017, Trends in Cognitive Sciences.

[7]  J. Cacioppo,et al.  Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation , 2017, Neuropsychopharmacology.

[8]  Chi-Hua Chen,et al.  Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders , 2016, Nature Genetics.

[9]  Peter K. Joshi,et al.  KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference , 2016, Proceedings of the National Academy of Sciences.

[10]  G. Willemsen,et al.  The Genetic Overlap Between Hair and Eye Color , 2016, Twin Research and Human Genetics.

[11]  Richard J. Smith Explanations for adaptations, just‐so stories, and limitations on evidence in evolutionary biology , 2016, Evolutionary anthropology.

[12]  A. Abdellaoui,et al.  Assortative mating on educational attainment leads to genetic spousal resemblance for polygenic scores , 2016 .

[13]  David M. Evans,et al.  A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts. , 2016, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  J. Cacioppo,et al.  Loneliness and implicit attention to social threat: A high-performance electrical neuroimaging study , 2016, Cognitive neuroscience.

[15]  P. Visscher,et al.  Genetic pleiotropy in complex traits and diseases: implications for genomic medicine , 2016, Genome Medicine.

[16]  D. Hinds,et al.  Identification of 15 genetic loci associated with risk of major depression in individuals of European descent , 2016, Nature Genetics.

[17]  Jonathan P. Beauchamp,et al.  Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses , 2016, Nature Genetics.

[18]  Jonathan P. Beauchamp,et al.  Genome-wide association study identifies 74 loci associated with educational attainment , 2016, Nature.

[19]  R. Marioni,et al.  Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank , 2016, Current Biology.

[20]  N. Eriksson,et al.  Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine , 2015, Nature Genetics.

[21]  Stuart J. Ritchie,et al.  Molecular genetic contributions to self-rated health , 2015, bioRxiv.

[22]  Toshiko Tanaka,et al.  Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium , 2015, Behavior Genetics.

[23]  P. Visscher,et al.  Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores , 2015, bioRxiv.

[24]  John T. Cacioppo,et al.  Implicit attention to negative social, in contrast to nonsocial, words in the Stroop task differs between individuals high and low in loneliness: Evidence from event-related brain microstates , 2015, Cortex.

[25]  Warren W. Kretzschmar,et al.  Sparse whole genome sequencing identifies two loci for major depressive disorder , 2015, Nature.

[26]  F. Rivadeneira,et al.  Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height , 2015, Behavior Genetics.

[27]  M. Daly,et al.  An Atlas of Genetic Correlations across Human Diseases and Traits , 2015, Nature Genetics.

[28]  Maarten M. Kampert,et al.  Sandwich corrected standard errors in family-based genome-wide association studies , 2014, European Journal of Human Genetics.

[29]  Stephanie Cacioppo,et al.  The neuroendocrinology of social isolation. , 2015, Annual review of psychology.

[30]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

[31]  I. Ntalla,et al.  A genome-wide association study of anorexia nervosa , 2011, Molecular Psychiatry.

[32]  S. Shoib,et al.  Relationship between loneliness, psychiatric disorders and physical health ? A review on the psychological aspects of loneliness. , 2014, Journal of clinical and diagnostic research : JCDR.

[33]  Rebecca R Andridge,et al.  Pain, depression, and fatigue: loneliness as a longitudinal risk factor. , 2014, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[34]  C. Spencer,et al.  Biological Insights From 108 Schizophrenia-Associated Genetic Loci , 2014, Nature.

[35]  Pieter B. T. Neerincx,et al.  Supplementary Information Whole-genome sequence variation , population structure and demographic history of the Dutch population , 2022 .

[36]  P. Sullivan,et al.  Effect of polygenic risk scores on depression in childhood trauma , 2014, British Journal of Psychiatry.

[37]  J. Cacioppo,et al.  Social Relationships and Health: The Toxic Effects of Perceived Social Isolation. , 2014, Social and personality psychology compass.

[38]  Stephanie Cacioppo,et al.  Evolutionary mechanisms for loneliness , 2014, Cognition & emotion.

[39]  S. Djurovic,et al.  Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia , 2013, Molecular Psychiatry.

[40]  Pieter B. T. Neerincx,et al.  The Genome of the Netherlands: design, and project goals , 2013, European Journal of Human Genetics.

[41]  Nick C Fox,et al.  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease , 2013, Nature Genetics.

[42]  P. Sullivan,et al.  Population structure, migration, and diversifying selection in the Netherlands , 2013, European Journal of Human Genetics.

[43]  Jianxin Shi,et al.  Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs , 2013, Nature Genetics.

[44]  Lisa M. Jaremka,et al.  Loneliness predicts pain, depression, and fatigue: Understanding the role of immune dysregulation , 2013, Psychoneuroendocrinology.

[45]  P. Visscher,et al.  Pitfalls of predicting complex traits from SNPs , 2013, Nature Reviews Genetics.

[46]  M. Daly,et al.  Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis , 2013, The Lancet.

[47]  L. Goossens,et al.  Personality traits, loneliness, and attitudes toward aloneness in adolescence , 2013 .

[48]  J. Wardle,et al.  Social isolation, loneliness, and all-cause mortality in older men and women , 2013, Proceedings of the National Academy of Sciences.

[49]  F. Dudbridge Power and Predictive Accuracy of Polygenic Risk Scores , 2013, PLoS genetics.

[50]  Michael F. Green,et al.  Social and nonsocial cognition in bipolar disorder and schizophrenia: relative levels of impairment. , 2013, The American journal of psychiatry.

[51]  H. M. Draisma,et al.  The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection , 2013, Twin Research and Human Genetics.

[52]  Wei Wang,et al.  MaCH‐Admix: Genotype Imputation for Admixed Populations , 2013, Genetic epidemiology.

[53]  P. Visscher,et al.  Genome-wide complex trait analysis (GCTA): methods, data analyses, and interpretations. , 2013, Methods in molecular biology.

[54]  H. Ben-Zur Loneliness, Optimism, and Well-Being Among Married, Divorced, and Widowed Individuals , 2012, The Journal of psychology.

[55]  H. Atak,et al.  Big Five Traits and Loneliness among Turkish Emerging Adults , 2012 .

[56]  A. Uutela,et al.  The effect of loneliness and change in loneliness on self-rated health (SRH): a longitudinal study among aging people. , 2011, Archives of gerontology and geriatrics.

[57]  L. Hawkley,et al.  A Meta-Analysis of Interventions to Reduce Loneliness , 2011, Personality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc.

[58]  P. Visscher,et al.  GCTA: a tool for genome-wide complex trait analysis. , 2011, American journal of human genetics.

[59]  L. Hawkley,et al.  Loneliness Matters: A Theoretical and Empirical Review of Consequences and Mechanisms , 2010, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[60]  Louise C Hawkley,et al.  Perceived social isolation makes me sad: 5-year cross-lagged analyses of loneliness and depressive symptomatology in the Chicago Health, Aging, and Social Relations Study. , 2010, Psychology and aging.

[61]  T. Lehner,et al.  The Netherlands Twin Register Biobank: A Resource for Genetic Epidemiological Studies , 2010, Twin Research and Human Genetics.

[62]  Ming D. Li,et al.  Genome-wide meta-analyses identify multiple loci associated with smoking behavior , 2010, Nature Genetics.

[63]  Dorret I. Boomsma,et al.  Familial Resemblance for Loneliness , 2010, Behavior genetics.

[64]  R. Plomin,et al.  Common disorders are quantitative traits , 2009, Nature Reviews Genetics.

[65]  L. Hawkley,et al.  Perceived social isolation and cognition , 2009, Trends in Cognitive Sciences.

[66]  P. Watson,et al.  The bright side of being blue: depression as an adaptation for analyzing complex problems. , 2009, Psychological review.

[67]  Jean Decety,et al.  In the Eye of the Beholder: Individual Differences in Perceived Social Isolation Predict Regional Brain Activation to Social Stimuli , 2009, Journal of Cognitive Neuroscience.

[68]  Louise C Hawkley,et al.  From social structural factors to perceptions of relationship quality and loneliness: the Chicago health, aging, and social relations study. , 2008, The journals of gerontology. Series B, Psychological sciences and social sciences.

[69]  T. Scharf,et al.  Loneliness in urban neighbourhoods: an Anglo-Dutch comparison , 2008, European journal of ageing.

[70]  Meike Bartels,et al.  Genetic and environmental contributions to stability in loneliness throughout childhood , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[71]  Peter Martin,et al.  The Indirect Influence of Educational Attainment on Loneliness among Unmarried Older Adults , 2007 .

[72]  L. Hawkley,et al.  Social regulation of gene expression in human leukocytes , 2007, Genome Biology.

[73]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[74]  J. Cacioppo,et al.  Longitudinal Genetic Analysis for Loneliness in Dutch Twins , 2007, Twin Research and Human Genetics.

[75]  John T. Cacioppo,et al.  Loneliness within a nomological net: An evolutionary perspective , 2006 .

[76]  E. Gullone,et al.  The clinical significance of loneliness: a literature review. , 2006, Clinical psychology review.

[77]  L. Hawkley,et al.  Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses. , 2006, Psychology and aging.

[78]  J. Cacioppo,et al.  Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24 , 2006, Behavior genetics.

[79]  Gonneke Willemsen,et al.  Genetic and Environmental Contributions to Loneliness in Adults: The Netherlands Twin Register Study , 2005, Behavior genetics.

[80]  R. Nesse,et al.  Is low mood an adaptation? Evidence for subtypes with symptoms that match precipitants. , 2005, Journal of Affective Disorders.

[81]  John T. Cacioppo,et al.  A Short Scale for Measuring Loneliness in Large Surveys , 2004, Research on aging.

[82]  N. Allen,et al.  The social risk hypothesis of depressed mood: evolutionary, psychosocial, and neurobiological perspectives. , 2003, Psychological bulletin.

[83]  J. Averill,et al.  Solitude: An Exploration of Benefits of Being Alone , 2003 .

[84]  S McGuire,et al.  Genetic and Environmental Contributions to Loneliness in Children , 2000, Psychological science.

[85]  Eric Turkheimer,et al.  Three Laws of Behavior Genetics and What They Mean , 2000 .

[86]  O. Kim The Effects of Loneliness on Alcohol Drinking, Smoking, and Health Perception in College Students , 1999 .

[87]  S. Duck,et al.  Loneliness and the Evaluation of Relational Events , 1994 .

[88]  I. Åkerlind,et al.  Loneliness and alcohol abuse: a review of evidences of an interplay. , 1992, Social science & medicine.

[89]  R. Page,et al.  Demographic Predictors of Self-Reported Loneliness in Adults , 1991, Psychological reports.

[90]  L. A. Peplau,et al.  Relation between loneliness and depression: a structural equation analysis. , 1980, Journal of personality and social psychology.

[91]  Letitia Anne Peplau,et al.  The Revised UCLA Loneliness Scale: Concurrent and Discriminant Validity Evidence , 1980 .

[92]  D. Russell,et al.  The revised UCLA Loneliness Scale: concurrent and discriminant validity evidence. , 1980, Journal of personality and social psychology.

[93]  R. Weiss,et al.  Loneliness: The Experience of Emotional and Social Isolation. , 1975 .