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

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...

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Detalles Bibliográficos
Autores: Andreu-Bernabeu, Álvaro, Díaz-Caneja, Covadonga M., Costas, Javier, De Hoyos, Lucía, Stella, Carol, Gurriarán, Xaquín, Alloza, Clara, Fañanás Saura, Lourdes, Bobes García, Julio, González-Pinto, Ana, Crespo-Facorro, Benedicto, Martorell, Lourdes, Vilella, Elisabet, Muntané, Gerard, Nacher, Juan, Moltó, M. Dolors, Aguilar, Eduardo Jesús, Parellada, Mara, Arango López, Celso, González-Peñas, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182648
Acceso en línea:https://hdl.handle.net/2445/182648
Access Level:acceso abierto
Palabra clave:Aïllament social
Esquizofrènia
Lleis de Mendel
Dones
Homes
Social isolation
Schizophrenia
Mendel's law
Women
Men
Descripción
Sumario: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.

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