Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

The METASTROKE Consortium of the International Stroke Genetics Consortium; The Netherlands Twin Registry; The neuroCHARGE Working Group; The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium; The 23 and Me Research Team; The Inflammation Working Group of the CHARGE Consortium; Daniel S. Tylee; Jiayin Sun; Jonathan L. Hess; Muhammad A. Tahir; Esha Sharma; Rainer Malik; Bradford B. Worrall; Andrew J. Levine; Jeremy J. Martinson; Sergey Nejentsev; Doug Speed; Annegret Fischer; Eric Mick; Brian R. Walker; Andrew Crawford; Struan F.A. Grant; Constantin Polychronakos; Jonathan P. Bradfield; Patrick M.A. Sleiman; Hakon Hakonarson; Eva Ellinghaus; James T. Elder; Lam C. Tsoi; Richard C. Trembath; Jonathan N. Barker; Andre Franke; Abbas Dehghan; Stephen V. Faraone; Stephen J. Glatt

doi:10.1002/ajmg.b.32652

Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, Daniel S. Tylee^*, Jiayin Sun, Jonathan L. Hess, Muhammad A. Tahir, Esha Sharma, Rainer Malik, Bradford B. Worrall, Andrew J. Levine, Jeremy J. Martinson, Sergey Nejentsev, Doug Speed, Annegret Fischer, Eric Mick, Brian R. WalkerAndrew Crawford, Struan F.A. Grant, Constantin Polychronakos, Jonathan P. Bradfield, Patrick M.A. Sleiman, Hakon Hakonarson, Eva Ellinghaus, James T. Elder, Lam C. Tsoi, Richard C. Trembath, Jonathan N. Barker, Andre Franke, Abbas Dehghan, Stephen V. Faraone, Stephen J. Glatt

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

149 Citations (Scopus)

Abstract

Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

Original language	English
Pages (from-to)	641-657
Number of pages	17
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	177
Issue number	7
Early online date	16 Oct 2018
DOIs	https://doi.org/10.1002/ajmg.b.32652
Publication status	Published - Oct 2018

Keywords

allergy
anorexia nervosa
attention deficit-hyperactivity disorder
autoimmune disorder
bipolar disorder
C-reactive protein
celiac disease
childhood ear infection
Crohn's disease
genetic correlation
genome-wide association
hypothyroidism
major depression
neuroticism
obsessive schizophrenia
primary biliary cirrhosis
rheumatoid arthritis
smoking
systemic lupus erythematosus
Tourette syndrome
tuberculosis susceptibility
type 1 diabetes
ulcerative colitis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ajmg.b.32652

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The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, Tylee, D. S., Sun, J., Hess, J. L., Tahir, M. A., Sharma, E., Malik, R., Worrall, B. B., Levine, A. J., Martinson, J. J., Nejentsev, S., Speed, D., Fischer, A., Mick, E., ... Glatt, S. J. (2018). Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 177(7), 641-657. https://doi.org/10.1002/ajmg.b.32652

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title = "Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data",

abstract = "Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.",

keywords = "allergy, anorexia nervosa, attention deficit-hyperactivity disorder, autoimmune disorder, bipolar disorder, C-reactive protein, celiac disease, childhood ear infection, Crohn's disease, genetic correlation, genome-wide association, hypothyroidism, major depression, neuroticism, obsessive schizophrenia, primary biliary cirrhosis, rheumatoid arthritis, smoking, systemic lupus erythematosus, Tourette syndrome, tuberculosis susceptibility, type 1 diabetes, ulcerative colitis",

author = "{The METASTROKE Consortium of the International Stroke Genetics Consortium} and {The Netherlands Twin Registry} and {The neuroCHARGE Working Group} and {The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium} and {The 23 and Me Research Team} and {The Inflammation Working Group of the CHARGE Consortium} and Tylee, {Daniel S.} and Jiayin Sun and Hess, {Jonathan L.} and Tahir, {Muhammad A.} and Esha Sharma and Rainer Malik and Worrall, {Bradford B.} and Levine, {Andrew J.} and Martinson, {Jeremy J.} and Sergey Nejentsev and Doug Speed and Annegret Fischer and Eric Mick and Walker, {Brian R.} and Andrew Crawford and Grant, {Struan F.A.} and Constantin Polychronakos and Bradfield, {Jonathan P.} and Sleiman, {Patrick M.A.} and Hakon Hakonarson and Eva Ellinghaus and Elder, {James T.} and Tsoi, {Lam C.} and Trembath, {Richard C.} and Barker, {Jonathan N.} and Andre Franke and Abbas Dehghan and Faraone, {Stephen V.} and Glatt, {Stephen J.}",

year = "2018",

month = oct,

doi = "10.1002/ajmg.b.32652",

language = "English",

volume = "177",

pages = "641--657",

journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley-Liss Inc.",

number = "7",

}

The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, Tylee, DS, Sun, J, Hess, JL, Tahir, MA, Sharma, E, Malik, R, Worrall, BB, Levine, AJ, Martinson, JJ, Nejentsev, S, Speed, D, Fischer, A, Mick, E, Walker, BR, Crawford, A, Grant, SFA, Polychronakos, C, Bradfield, JP, Sleiman, PMA, Hakonarson, H, Ellinghaus, E, Elder, JT, Tsoi, LC, Trembath, RC , Barker, JN, Franke, A, Dehghan, A, Faraone, SV & Glatt, SJ 2018, 'Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 177, no. 7, pp. 641-657. https://doi.org/10.1002/ajmg.b.32652

Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. / The METASTROKE Consortium of the International Stroke Genetics Consortium; The Netherlands Twin Registry; The neuroCHARGE Working Group et al.
In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 177, No. 7, 10.2018, p. 641-657.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

AU - The METASTROKE Consortium of the International Stroke Genetics Consortium

AU - The Netherlands Twin Registry

AU - The neuroCHARGE Working Group

AU - The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium

AU - The 23 and Me Research Team

AU - The Inflammation Working Group of the CHARGE Consortium

AU - Tylee, Daniel S.

AU - Sun, Jiayin

AU - Hess, Jonathan L.

AU - Tahir, Muhammad A.

AU - Sharma, Esha

AU - Malik, Rainer

AU - Worrall, Bradford B.

AU - Levine, Andrew J.

AU - Martinson, Jeremy J.

AU - Nejentsev, Sergey

AU - Speed, Doug

AU - Fischer, Annegret

AU - Mick, Eric

AU - Walker, Brian R.

AU - Crawford, Andrew

AU - Grant, Struan F.A.

AU - Polychronakos, Constantin

AU - Bradfield, Jonathan P.

AU - Sleiman, Patrick M.A.

AU - Hakonarson, Hakon

AU - Ellinghaus, Eva

AU - Elder, James T.

AU - Tsoi, Lam C.

AU - Trembath, Richard C.

AU - Barker, Jonathan N.

AU - Franke, Andre

AU - Dehghan, Abbas

AU - Faraone, Stephen V.

AU - Glatt, Stephen J.

PY - 2018/10

Y1 - 2018/10

N2 - Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

AB - Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

KW - allergy

KW - anorexia nervosa

KW - attention deficit-hyperactivity disorder

KW - autoimmune disorder

KW - bipolar disorder

KW - C-reactive protein

KW - celiac disease

KW - childhood ear infection

KW - Crohn's disease

KW - genetic correlation

KW - genome-wide association

KW - hypothyroidism

KW - major depression

KW - neuroticism

KW - obsessive schizophrenia

KW - primary biliary cirrhosis

KW - rheumatoid arthritis

KW - smoking

KW - systemic lupus erythematosus

KW - Tourette syndrome

KW - tuberculosis susceptibility

KW - type 1 diabetes

KW - ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=85055056349&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32652

DO - 10.1002/ajmg.b.32652

M3 - Article

C2 - 30325587

AN - SCOPUS:85055056349

SN - 1552-4841

VL - 177

SP - 641

EP - 657

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 7

ER -

The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium et al. Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2018 Oct;177(7):641-657. Epub 2018 Oct 16. doi: 10.1002/ajmg.b.32652

Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

Abstract

Keywords

UN SDGs

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