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

被引：18

作者：

Andreu-Bernabeu, Alvaro ^{[1
,2
]}

Diaz-Caneja, Covadonga M. ^{[1
,2
,3
,4
]}

Costas, Javier ^{[5
]}

De Hoyos, Lucia ^{[1
,2
]}

Stella, Carol ^{[1
,2
]}

Gurriaran, Xaquin ^{[1
,2
,5
]}

Alloza, Clara ^{[1
,2
]}

Fananas, Lourdes ^{[3
,6
]}

Bobes, Julio ^{[3
,7
]}

Gonzalez-Pinto, Ana ^{[3
,8
]}

Crespo-Facorro, Benedicto ^{[3
,9
]}

Martorell, Lourdes ^{[3
,10
]}

Vilella, Elisabet ^{[3
,10
]}

Muntane, Gerard ^{[3
,10
]}

Nacher, Juan ^{[3
,11
]}

Dolores Molto, Maria ^{[3
,12
,13
]}

Jesus Aguilar, Eduardo ^{[3
,13
,14
]}

Parellada, Mara ^{[1
,2
,3
,4
]}

Arango, Celso ^{[1
,2
,3
,4
]}

Gonzalez-Penas, Javier ^{[1
,2
,3
]}

机构：

[1] Hosp Gen Univ Gregorio Maranon, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid, Spain

[2] Inst Invest Sanitaria Gregorio Maranon IiSGM, Madrid, Spain

[3] Ctr Invest Biomed Red Salud Mental, CIBERSAM, Madrid, Spain

[4] Univ Complutense, Sch Med, Madrid, Spain

[5] Complexo Hosp Univ Santiago de Compostela CHUS, Serv Galego Saude SERGAS, Inst Invest Sanitaria IDIS Santiago de Compostela, Santiago De Compostela, Galicia, Spain

[6] Univ Barcelona, Fac Biol, Dept Evolutionary Biol Ecol & Environm Sci, Barcelona, Spain

[7] Univ Oviedo, ISPA, INEUROPA, Fac Med & Hlth Sci Psychiat, Oviedo, Spain

[8] Univ Basque Country, Univ Hosp, OSI Araba, BIOARABA Hlth Res Inst, Vitoria, Spain

[9] Univ Seville, Dept Psychiat, Hosp Univ Virgen del Rocio, Seville, Spain

[10] Univ Rovira & Virgili, IISPV, Hosp Univ Inst Pere Mata, Reus, Spain

[11] Univ Valencia, Dept Cell Biol Interdisciplinary Res Struct Biote, Neurobiol Unit, Valencia 46100, Spain

[12] Univ Valencia, Dept Genet, Campus Burjassot, Valencia, Spain

[13] Univ Valencia, Dept Med, Valencia, Spain

[14] Fdn Invest Hosp Clin Valencia, INCLIVA, Valencia 46010, Spain

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

关键词：

GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; GENDER-DIFFERENCES; SCORE REGRESSION; RISK; PSYCHOSIS; DEPRESSION; HERITABILITY; PREVALENCE; MORTALITY;

D O I：

10.1038/s41467-021-27598-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 92 条

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