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

Author

Listed:
  • Álvaro Andreu-Bernabeu

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))

  • Covadonga M. Díaz-Caneja

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
    CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universidad Complutense)

  • Javier Costas

    (Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela)

  • Lucía De Hoyos

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))

  • Carol Stella

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))

  • Xaquín Gurriarán

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
    Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela)

  • Clara Alloza

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))

  • Lourdes Fañanás

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    University of Barcelona)

  • Julio Bobes

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universidad de Oviedo, ISPA, INEUROPA)

  • Ana González-Pinto

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    University of the Basque Country)

  • Benedicto Crespo-Facorro

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universidad de Sevilla)

  • Lourdes Martorell

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universitat Rovira i Virgili)

  • Elisabet Vilella

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universitat Rovira i Virgili)

  • Gerard Muntané

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universitat Rovira i Virgili)

  • Juan Nacher

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    University of Valencia)

  • María Dolores Molto

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    University of Valencia, Campus of Burjassot
    Universitat de València)

  • Eduardo Jesús Aguilar

    (CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universitat de València
    Fundación Investigación Hospital Clínico de Valencia, INCLIVA)

  • Mara Parellada

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
    CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universidad Complutense)

  • Celso Arango

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
    CIBERSAM, Centro Investigación Biomédica en Red Salud Mental
    Universidad Complutense)

  • Javier González-Peñas

    (Hospital General Universitario Gregorio Marañón
    Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)
    CIBERSAM, Centro Investigación Biomédica en Red Salud Mental)

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.

Suggested Citation

  • Álvaro Andreu-Bernabeu & Covadonga M. Díaz-Caneja & Javier Costas & Lucía De Hoyos & Carol Stella & Xaquín Gurriarán & Clara Alloza & Lourdes Fañanás & Julio Bobes & Ana González-Pinto & Benedicto Cre, 2022. "Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27598-6
    DOI: 10.1038/s41467-021-27598-6
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