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

• DOI: 10.1038/s41467-021-27598-6
• Publication Date: 2022-01-10T11:02:59Z
• Authors: Álvaro Andreu-Ber...; Covadonga M. Díaz...; Javier Costas; Lucía De Hoyos; Carol Stella; Xaquín Gurriarán; Clara Alloza; Lourdes Fañanás; Julio Bobes; Ana González-Pinto; Benedicto Crespo-...; Lourdes Martorell; Elisabet Vilella; Gerard Muntané; Juan Nacher; María Dolores Molto; Eduardo Jesús Agu...; Mara Parellada; Celso Arango; Javier González-P...
• Keywords: Polygenic risk score; Mendelian Randomization

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 independent case-control sample (N = 3,488). We then subset predisposing variation based on its effect LNL-ISO. find that genetic concordant effects both phenotypes shows significant SNP-based heritability enrichment, higher females, positive covariance mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, autism. Conversely, discordant only contributes males is negatively correlated those disorders. Mendelian randomization analyses plausible bi-directional causal relationship between schizophrenia, greater liability than vice versa. These results illustrate the footprint