Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

doi:10.1038/s42003-018-0155-y

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

Medicine

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

14 Citas (Scopus)

Resumen

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

Idioma original	English
Número de artículo	163
Publicación	Communications Biology
Volumen	1
N.º	1
DOI	https://doi.org/10.1038/s42003-018-0155-y
Estado	Published - dic. 1 2018

Nota bibliográfica

Funding Information:
We would like to thank the family members for their enthusiastic participation. We thank our ethics consultant Prof. Barbara Prainsack for insightful discussions. This paper represents independent research part-funded by FAPESP (2014/50830-2; 2010/08968-6), the Marie Curie International Research Staff Exchange (FP7-PEOPLE-2011-IRSES/ 295192), and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. SDJ is funded by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant IF 658195. S.J.N. is also supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, and by awards establishing the Farr Institute of Health Informatics Research at UCLPartners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (grant MR/K006584/1). The views expressed are those of the authors and not necessarily those of the EU, the NHS, the NIHR or the Department of Health.

Funding Information:
Competing Interests: G.B. has been a consultant in preclinical genomics and has received grant funding from Eli Lilly ltd within the last 3 years. A.G. has participated in advisory boards for Janssen-Cilag and Daiichi-Sankyo. The remaining authors declare no competing interests.

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus Subject Areas

Medicine (miscellaneous)
General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

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10.1038/s42003-018-0155-y

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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. / Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium.
En: Communications Biology, Vol. 1, N.º 1, 163, 01.12.2018.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

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title = "Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder",

abstract = "Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.",

author = "{Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium} and {de Jong}, Simone and Diniz, {Mateus Jose Abdalla} and Andiara Saloma and Ary Gadelha and Santoro, {Marcos L.} and Ota, {Vanessa K.} and Cristiano Noto and Wray, {Naomi R.} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, {Enda M.} and Abdel Abdellaoui and Adams, {Mark J.} and Esben Agerbo and Air, {Tracy M.} and Andlauer, {Till F.M.} and Bacanu, {Silviu Alin} and Marie B{\ae}kvad-Hansen and Beekman, {Aartjan T.F.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Blackwood, {Douglas H.R.} and Julien Bryois and Buttensch{\o}n, {Henriette N.} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, {Jane Hvarregaard} and Clarke, {Toni Kim} and Coleman, {Jonathan R.I.} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, {Gregory E.} and Gail Davies and Deary, {Ian J.} and Franziska Degenhardt and Derks, {Eske M.} and Nese Direk and Dolan, {Conor V.} and Dunn, {Erin C.} and Eley, {Thalia C.} and Valentina Escott-Price and Kiadeh, {Farnush Farhadi Hassan} and Finucane, {Hilary K.} and Forstner, {Andreas J.} and Josef Frank and Rudolf Uher and Sandra Meier",

note = "Funding Information: We would like to thank the family members for their enthusiastic participation. We thank our ethics consultant Prof. Barbara Prainsack for insightful discussions. This paper represents independent research part-funded by FAPESP (2014/50830-2; 2010/08968-6), the Marie Curie International Research Staff Exchange (FP7-PEOPLE-2011-IRSES/ 295192), and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. SDJ is funded by the European Union{\textquoteright}s Horizon 2020 research and innovation programme under Marie Sk{\l}odowska-Curie grant IF 658195. S.J.N. is also supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, and by awards establishing the Farr Institute of Health Informatics Research at UCLPartners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (grant MR/K006584/1). The views expressed are those of the authors and not necessarily those of the EU, the NHS, the NIHR or the Department of Health. Funding Information: Competing Interests: G.B. has been a consultant in preclinical genomics and has received grant funding from Eli Lilly ltd within the last 3 years. A.G. has participated in advisory boards for Janssen-Cilag and Daiichi-Sankyo. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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doi = "10.1038/s42003-018-0155-y",

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AU - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium

AU - de Jong, Simone

AU - Diniz, Mateus Jose Abdalla

AU - Saloma, Andiara

AU - Gadelha, Ary

AU - Santoro, Marcos L.

AU - Ota, Vanessa K.

AU - Noto, Cristiano

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H.R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Uher, Rudolf

AU - Meier, Sandra

N1 - Funding Information: We would like to thank the family members for their enthusiastic participation. We thank our ethics consultant Prof. Barbara Prainsack for insightful discussions. This paper represents independent research part-funded by FAPESP (2014/50830-2; 2010/08968-6), the Marie Curie International Research Staff Exchange (FP7-PEOPLE-2011-IRSES/ 295192), and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. SDJ is funded by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant IF 658195. S.J.N. is also supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, and by awards establishing the Farr Institute of Health Informatics Research at UCLPartners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (grant MR/K006584/1). The views expressed are those of the authors and not necessarily those of the EU, the NHS, the NIHR or the Department of Health. Funding Information: Competing Interests: G.B. has been a consultant in preclinical genomics and has received grant funding from Eli Lilly ltd within the last 3 years. A.G. has participated in advisory boards for Janssen-Cilag and Daiichi-Sankyo. The remaining authors declare no competing interests. Publisher Copyright: © 2018, The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

AB - Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

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