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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. / Schizophrenia Working Group of the Psychiatric Genomics Consortium.

In: Biological Psychiatry, 23.03.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Schizophrenia Working Group of the Psychiatric Genomics Consortium 2021, 'Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders', Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2021.02.972

APA

Schizophrenia Working Group of the Psychiatric Genomics Consortium (2021). Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2021.02.972

CBE

Schizophrenia Working Group of the Psychiatric Genomics Consortium. 2021. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2021.02.972

MLA

Schizophrenia Working Group of the Psychiatric Genomics Consortium. "Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders". Biological Psychiatry. 2021. https://doi.org/10.1016/j.biopsych.2021.02.972

Vancouver

Schizophrenia Working Group of the Psychiatric Genomics Consortium. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry. 2021 Mar 23. https://doi.org/10.1016/j.biopsych.2021.02.972

Author

Schizophrenia Working Group of the Psychiatric Genomics Consortium. / Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. In: Biological Psychiatry. 2021.

Bibtex

@article{681d848f22824fb9808cda9953f43dc9,
title = "Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders",
abstract = "BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.",
author = "Blokland, {Gabri{\"e}lla A M} and Jakob Grove and Chia-Yen Chen and Chris Cotsapas and Stuart Tobet and Robert Handa and {St Clair}, David and Todd Lencz and Mowry, {Bryan J} and Sathish Periyasamy and Cairns, {Murray J} and Tooney, {Paul A} and Wu, {Jing Qin} and Brian Kelly and George Kirov and Sullivan, {Patrick F} and Aiden Corvin and Riley, {Brien P} and T{\~o}nu Esko and Lili Milani and J{\"o}nsson, {Erik G} and Aarno Palotie and Hannelore Ehrenreich and Martin Begemann and Agnes Steixner-Kumar and Sham, {Pak C} and Nakao Iwata and Weinberger, {Daniel R} and Gejman, {Pablo V} and Sanders, {Alan R} and Buxbaum, {Joseph D} and Dan Rujescu and Ina Giegling and Bettina Konte and Hartmann, {Annette M} and Elvira Bramon and Murray, {Robin M} and Pato, {Michele T} and Jimmy Lee and Ingrid Melle and Espen Molden and Ophoff, {Roel A} and Andrew McQuillin and Bass, {Nicholas J} and Rolf Adolfsson and Malhotra, {Anil K} and Ole Mors and Mortensen, {Preben B} and Als, {Thomas D} and B{\o}rglum, {Anders D} and {Schizophrenia Working Group of the Psychiatric Genomics Consortium}",
note = "Copyright {\textcopyright} 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = mar,
day = "23",
doi = "10.1016/j.biopsych.2021.02.972",
language = "English",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

AU - Blokland, Gabriëlla A M

AU - Grove, Jakob

AU - Chen, Chia-Yen

AU - Cotsapas, Chris

AU - Tobet, Stuart

AU - Handa, Robert

AU - St Clair, David

AU - Lencz, Todd

AU - Mowry, Bryan J

AU - Periyasamy, Sathish

AU - Cairns, Murray J

AU - Tooney, Paul A

AU - Wu, Jing Qin

AU - Kelly, Brian

AU - Kirov, George

AU - Sullivan, Patrick F

AU - Corvin, Aiden

AU - Riley, Brien P

AU - Esko, Tõnu

AU - Milani, Lili

AU - Jönsson, Erik G

AU - Palotie, Aarno

AU - Ehrenreich, Hannelore

AU - Begemann, Martin

AU - Steixner-Kumar, Agnes

AU - Sham, Pak C

AU - Iwata, Nakao

AU - Weinberger, Daniel R

AU - Gejman, Pablo V

AU - Sanders, Alan R

AU - Buxbaum, Joseph D

AU - Rujescu, Dan

AU - Giegling, Ina

AU - Konte, Bettina

AU - Hartmann, Annette M

AU - Bramon, Elvira

AU - Murray, Robin M

AU - Pato, Michele T

AU - Lee, Jimmy

AU - Melle, Ingrid

AU - Molden, Espen

AU - Ophoff, Roel A

AU - McQuillin, Andrew

AU - Bass, Nicholas J

AU - Adolfsson, Rolf

AU - Malhotra, Anil K

AU - Mors, Ole

AU - Mortensen, Preben B

AU - Als, Thomas D

AU - Børglum, Anders D

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

N1 - Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2021/3/23

Y1 - 2021/3/23

N2 - BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

AB - BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

U2 - 10.1016/j.biopsych.2021.02.972

DO - 10.1016/j.biopsych.2021.02.972

M3 - Journal article

C2 - 34099189

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

ER -