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Applying polygenic risk scoring for psychiatric disorders to a large family with Bipolar Disorder and Major Depressive Disorder

View ORCID ProfileSimone de Jong, Mateus Jose Abdalla Diniz, Andiara Calado Saloma Rodrigues, Ary Gadelha, Marcos L Santoro, Vanessa K Ota, Cristiano Noto, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Charles Curtis, Hamel Patel, Lynsey S Hall, Paul F O’Reilly, Sintia I Belangero, Rodrigo Bressan, Gerome Breen
doi: https://doi.org/10.1101/103713
Simone de Jong
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom
2National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
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  • ORCID record for Simone de Jong
Mateus Jose Abdalla Diniz
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
4Pax Clinica Psiquiatrica, Rodovia Br153, Santa Luzia - Aparecida de Goiânia/GO CEP: 74922-810
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Andiara Calado Saloma Rodrigues
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
4Pax Clinica Psiquiatrica, Rodovia Br153, Santa Luzia - Aparecida de Goiânia/GO CEP: 74922-810
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Ary Gadelha
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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Marcos L Santoro
5Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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Vanessa K Ota
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
5Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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Cristiano Noto
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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6Full list of Consortium members is given in Supplementary Information S1
Charles Curtis
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom
2National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
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Hamel Patel
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom
2National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
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Lynsey S Hall
7Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom
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Paul F O’Reilly
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom
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Sintia I Belangero
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
5Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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Rodrigo Bressan
3Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil
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Gerome Breen
1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom
2National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
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  • For correspondence: gerome.breen@gmail.com
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ABSTRACT

We aim to investigate the application of polygenic risk scoring within a family context. Polygenic risk profiles could aid in unraveling the role that common variation confers on disease risk within a pedigree that would have traditionally been viewed through the prism of monogenic inheritance only. We illustrate our discussion by analyzing polygenic risk scores for schizophrenia, major depressive disorder and bipolar disorder in a large pedigree (n~260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. We apply polygenic risk scores to study patterns of assortative mating and anticipation, whereby it appears increased polygenic risk for psychiatric disorders is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations in the family. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity of a disease increases over the generations of a family. Joint analyses of both rare and common variation may be the most powerful way to understand the familial genetics of mood and psychiatric disorders.

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Posted February 06, 2018.
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Applying polygenic risk scoring for psychiatric disorders to a large family with Bipolar Disorder and Major Depressive Disorder
Simone de Jong, Mateus Jose Abdalla Diniz, Andiara Calado Saloma Rodrigues, Ary Gadelha, Marcos L Santoro, Vanessa K Ota, Cristiano Noto, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Charles Curtis, Hamel Patel, Lynsey S Hall, Paul F O’Reilly, Sintia I Belangero, Rodrigo Bressan, Gerome Breen
bioRxiv 103713; doi: https://doi.org/10.1101/103713
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Applying polygenic risk scoring for psychiatric disorders to a large family with Bipolar Disorder and Major Depressive Disorder
Simone de Jong, Mateus Jose Abdalla Diniz, Andiara Calado Saloma Rodrigues, Ary Gadelha, Marcos L Santoro, Vanessa K Ota, Cristiano Noto, Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium, Charles Curtis, Hamel Patel, Lynsey S Hall, Paul F O’Reilly, Sintia I Belangero, Rodrigo Bressan, Gerome Breen
bioRxiv 103713; doi: https://doi.org/10.1101/103713

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