Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

S Hong Lee, Stephan Ripke, Benjamin M Neale, Stephen V Faraone, Shaun M Purcell, Roy H Perlis, Bryan J Mowry, Anita Thapar, Michael E Goddard, John S Witte, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A Andreassen, Adebayo Anjorin, Richard Anney, Verneri Anttila, Dan E Arking, Philip Asherson & 31 others Maria H Azevedo, Lena Backlund, Judith A Badner, Anthony J Bailey, Tobias Banaschewski, Jack D Barchas, Michael R Barnes, Thomas B Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B Binder, Donald W Black, Douglas H R Blackwood, Cinnamon S Bloss, Michael Boehnke, Dorret I Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Paul Cormican, Nancy G Buccola, Benjamin S Pickard, Cross-Disorder Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

1097 Citations (Scopus)

Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
LanguageEnglish
Pages984–994
Number of pages11
JournalNature Genetics
Volume45
Issue number9
Early online date28 Aug 2013
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Major Depressive Disorder
Single Nucleotide Polymorphism
Psychiatry
Schizophrenia
Bipolar Disorder
Genome
Attention Deficit Disorder with Hyperactivity
Genomics
Crohn Disease
Genotype
Autism Spectrum Disorder

Keywords

  • pathophysiology
  • Psychiatric Genomics Consortium
  • genotype data
  • psychiatric disorders

Cite this

Lee, S. H., Ripke, S., Neale, B. M., Faraone, S. V., Purcell, S. M., Perlis, R. H., ... Cross-Disorder Group of the Psychiatric Genomics Consortium (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984–994. https://doi.org/10.1038/ng.2711
Lee, S Hong ; Ripke, Stephan ; Neale, Benjamin M ; Faraone, Stephen V ; Purcell, Shaun M ; Perlis, Roy H ; Mowry, Bryan J ; Thapar, Anita ; Goddard, Michael E ; Witte, John S ; Absher, Devin ; Agartz, Ingrid ; Akil, Huda ; Amin, Farooq ; Andreassen, Ole A ; Anjorin, Adebayo ; Anney, Richard ; Anttila, Verneri ; Arking, Dan E ; Asherson, Philip ; Azevedo, Maria H ; Backlund, Lena ; Badner, Judith A ; Bailey, Anthony J ; Banaschewski, Tobias ; Barchas, Jack D ; Barnes, Michael R ; Barrett, Thomas B ; Bass, Nicholas ; Battaglia, Agatino ; Bauer, Michael ; Bayés, Mònica ; Bellivier, Frank ; Bergen, Sarah E ; Berrettini, Wade ; Betancur, Catalina ; Bettecken, Thomas ; Biederman, Joseph ; Binder, Elisabeth B ; Black, Donald W ; Blackwood, Douglas H R ; Bloss, Cinnamon S ; Boehnke, Michael ; Boomsma, Dorret I ; Breen, Gerome ; Breuer, René ; Bruggeman, Richard ; Cormican, Paul ; Buccola, Nancy G ; Pickard, Benjamin S ; Cross-Disorder Group of the Psychiatric Genomics Consortium. / Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. In: Nature Genetics. 2013 ; Vol. 45, No. 9. pp. 984–994.
@article{d181ef14338040cab38727cc00be3334,
title = "Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs",
abstract = "Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29{\%} of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.",
keywords = "pathophysiology, Psychiatric Genomics Consortium , genotype data, psychiatric disorders",
author = "Lee, {S Hong} and Stephan Ripke and Neale, {Benjamin M} and Faraone, {Stephen V} and Purcell, {Shaun M} and Perlis, {Roy H} and Mowry, {Bryan J} and Anita Thapar and Goddard, {Michael E} and Witte, {John S} and Devin Absher and Ingrid Agartz and Huda Akil and Farooq Amin and Andreassen, {Ole A} and Adebayo Anjorin and Richard Anney and Verneri Anttila and Arking, {Dan E} and Philip Asherson and Azevedo, {Maria H} and Lena Backlund and Badner, {Judith A} and Bailey, {Anthony J} and Tobias Banaschewski and Barchas, {Jack D} and Barnes, {Michael R} and Barrett, {Thomas B} and Nicholas Bass and Agatino Battaglia and Michael Bauer and M{\`o}nica Bay{\'e}s and Frank Bellivier and Bergen, {Sarah E} and Wade Berrettini and Catalina Betancur and Thomas Bettecken and Joseph Biederman and Binder, {Elisabeth B} and Black, {Donald W} and Blackwood, {Douglas H R} and Bloss, {Cinnamon S} and Michael Boehnke and Boomsma, {Dorret I} and Gerome Breen and Ren{\'e} Breuer and Richard Bruggeman and Paul Cormican and Buccola, {Nancy G} and Pickard, {Benjamin S} and {Cross-Disorder Group of the Psychiatric Genomics Consortium}",
year = "2013",
month = "9",
doi = "10.1038/ng.2711",
language = "English",
volume = "45",
pages = "984–994",
journal = "Nature Genetics",
issn = "1061-4036",
number = "9",

}

Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DHR, Bloss, CS, Boehnke, M, Boomsma, DI, Breen, G, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Pickard, BS & Cross-Disorder Group of the Psychiatric Genomics Consortium 2013, 'Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs' Nature Genetics, vol. 45, no. 9, pp. 984–994. https://doi.org/10.1038/ng.2711

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. / Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Pickard, Benjamin S; Cross-Disorder Group of the Psychiatric Genomics Consortium.

In: Nature Genetics, Vol. 45, No. 9, 09.2013, p. 984–994.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

AU - Lee, S Hong

AU - Ripke, Stephan

AU - Neale, Benjamin M

AU - Faraone, Stephen V

AU - Purcell, Shaun M

AU - Perlis, Roy H

AU - Mowry, Bryan J

AU - Thapar, Anita

AU - Goddard, Michael E

AU - Witte, John S

AU - Absher, Devin

AU - Agartz, Ingrid

AU - Akil, Huda

AU - Amin, Farooq

AU - Andreassen, Ole A

AU - Anjorin, Adebayo

AU - Anney, Richard

AU - Anttila, Verneri

AU - Arking, Dan E

AU - Asherson, Philip

AU - Azevedo, Maria H

AU - Backlund, Lena

AU - Badner, Judith A

AU - Bailey, Anthony J

AU - Banaschewski, Tobias

AU - Barchas, Jack D

AU - Barnes, Michael R

AU - Barrett, Thomas B

AU - Bass, Nicholas

AU - Battaglia, Agatino

AU - Bauer, Michael

AU - Bayés, Mònica

AU - Bellivier, Frank

AU - Bergen, Sarah E

AU - Berrettini, Wade

AU - Betancur, Catalina

AU - Bettecken, Thomas

AU - Biederman, Joseph

AU - Binder, Elisabeth B

AU - Black, Donald W

AU - Blackwood, Douglas H R

AU - Bloss, Cinnamon S

AU - Boehnke, Michael

AU - Boomsma, Dorret I

AU - Breen, Gerome

AU - Breuer, René

AU - Bruggeman, Richard

AU - Cormican, Paul

AU - Buccola, Nancy G

AU - Pickard, Benjamin S

AU - Cross-Disorder Group of the Psychiatric Genomics Consortium

PY - 2013/9

Y1 - 2013/9

N2 - Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

AB - Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

KW - pathophysiology

KW - Psychiatric Genomics Consortium

KW - genotype data

KW - psychiatric disorders

U2 - 10.1038/ng.2711

DO - 10.1038/ng.2711

M3 - Article

VL - 45

SP - 984

EP - 994

JO - Nature Genetics

T2 - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics. 2013 Sep;45(9):984–994. https://doi.org/10.1038/ng.2711