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Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia.

ABSTRACT: Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia.

SUBMITTER: Andreu-Bernabeu A

PROVIDER: S-EPMC8748758 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia.

Andreu-Bernabeu Álvaro Á Díaz-Caneja Covadonga M CM Costas Javier J De Hoyos Lucía L Stella Carol C Gurriarán Xaquín X Alloza Clara C Fañanás Lourdes L Bobes Julio J González-Pinto Ana A Crespo-Facorro Benedicto B Martorell Lourdes L Vilella Elisabet E Muntané Gerard G Nacher Juan J Molto María Dolores MD Aguilar Eduardo Jesús EJ Parellada Mara M Arango Celso C González-Peñas Javier J

Nature communications 20220110 1

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and pos ...[more]

PMID: 35013163

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Project description:BackgroundSmoking is often colloquially considered "social". However, the actual relationship of smoking with current and future social isolation and loneliness is unclear. We therefore examined these relationships over a 12-year follow-up.MethodsIn this cohort study, we used a nationally representative sample of community dwelling adults aged 50 years and over from the English Longitudinal Study of Ageing (N=8780) (45% male, mean(SD) age 67(10) years. We examined associations of self-reported smoking status at baseline assessment, with social isolation (low social contact, social disengagement, domestic isolation), and loneliness (3-item UCLA loneliness scale), measured at baseline, and follow-up at 4, 8 and 12 years, using ordinary least squares regression models.FindingsAt baseline, smokers were more likely to be lonely (coef.=0·111, 95% CI 0·025 - 0·196) and socially isolated than non-smokers, having less frequent social interactions with family and friends (coef.= 0·297, 95%CI 0·148 - 0·446), less frequent engagement with community and cultural activities (coef.= 0·534, 95%CI 0·421 - 0·654), and being more likely to live alone (Odds Ratio =1·400, 95%CI 1·209 - 1·618). Smoking at baseline was associated with larger reductions in social contact (coef.=0·205, 95%CI 0·053 - 0·356, to 0·297, 95%CI 0·140 - 0·455), increases in social disengagement (coef.=0·168, 95%CI 0·066 - 0·270, to coef.=0·197, 95%CI 0·087 - 0·307), and increases in loneliness (coef.=0·105, 95%CI 0·003 - 0·207), at 4-year follow-up) over time. No association was found between smoking and changes in cohabitation status. Findings were independent of all identified confounders, including age, sex, social class and the presence of physical and mental health diagnoses.InterpretationSmoking is associated with the development of increasing social isolation and loneliness in older adults, suggesting smoking is detrimental to aspects of psychosocial health. The idea that smoking might be prosocial appears a misconception.FundingUK Economic and Social Research Council & Imperial College London.

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Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia.

Publications

Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia.

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