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Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits

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Harvard

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium 2021, 'Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits', Biological Psychiatry, vol. 89, no. 12, pp. 1127-1137. https://doi.org/10.1016/j.biopsych.2020.12.024

APA

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium (2021). Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. Biological Psychiatry, 89(12), 1127-1137. https://doi.org/10.1016/j.biopsych.2020.12.024

CBE

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium. 2021. Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. Biological Psychiatry. 89(12):1127-1137. https://doi.org/10.1016/j.biopsych.2020.12.024

MLA

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium. "Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits". Biological Psychiatry. 2021, 89(12). 1127-1137. https://doi.org/10.1016/j.biopsych.2020.12.024

Vancouver

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium. Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. Biological Psychiatry. 2021 Jun 15;89(12):1127-1137. https://doi.org/10.1016/j.biopsych.2020.12.024

Author

Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium. / Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. In: Biological Psychiatry. 2021 ; Vol. 89, No. 12. pp. 1127-1137.

Bibtex

@article{00cb51eef48546998c73434ea499b746,
title = "Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits",
abstract = "BACKGROUND: The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.METHODS: Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.RESULTS: We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior).CONCLUSIONS: Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.",
keywords = "Behavioral, Genetic correlation, GWAS, Heritability, Psychiatric, Sex differences",
author = "Joanna Martin and Khramtsova, {Ekaterina A} and Goleva, {Slavina B} and Blokland, {Gabri{\"e}lla A M} and Michela Traglia and Walters, {Raymond K} and Christopher H{\"u}bel and Coleman, {Jonathan R I} and Gerome Breen and B{\o}rglum, {Anders D} and Ditte Demontis and Jakob Grove and Thomas Werge and Janita Bralten and Bulik, {Cynthia M} and Lee, {Phil H} and Mathews, {Carol A} and Peterson, {Roseann E} and Winham, {Stacey J} and Naomi Wray and Edenberg, {Howard J} and Wei Guo and Yin Yao and Neale, {Benjamin M} and Faraone, {Stephen V} and Petryshen, {Tracey L} and Weiss, {Lauren A} and Duncan, {Laramie E} and Goldstein, {Jill M} and Smoller, {Jordan W} and Stranger, {Barbara E} and Davis, {Lea K} and {Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium}",
note = "Copyright {\textcopyright} 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = jun,
day = "15",
doi = "10.1016/j.biopsych.2020.12.024",
language = "English",
volume = "89",
pages = "1127--1137",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier Inc",
number = "12",

}

RIS

TY - JOUR

T1 - Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits

AU - Martin, Joanna

AU - Khramtsova, Ekaterina A

AU - Goleva, Slavina B

AU - Blokland, Gabriëlla A M

AU - Traglia, Michela

AU - Walters, Raymond K

AU - Hübel, Christopher

AU - Coleman, Jonathan R I

AU - Breen, Gerome

AU - Børglum, Anders D

AU - Demontis, Ditte

AU - Grove, Jakob

AU - Werge, Thomas

AU - Bralten, Janita

AU - Bulik, Cynthia M

AU - Lee, Phil H

AU - Mathews, Carol A

AU - Peterson, Roseann E

AU - Winham, Stacey J

AU - Wray, Naomi

AU - Edenberg, Howard J

AU - Guo, Wei

AU - Yao, Yin

AU - Neale, Benjamin M

AU - Faraone, Stephen V

AU - Petryshen, Tracey L

AU - Weiss, Lauren A

AU - Duncan, Laramie E

AU - Goldstein, Jill M

AU - Smoller, Jordan W

AU - Stranger, Barbara E

AU - Davis, Lea K

AU - Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium

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

PY - 2021/6/15

Y1 - 2021/6/15

N2 - BACKGROUND: The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.METHODS: Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.RESULTS: We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior).CONCLUSIONS: Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.

AB - BACKGROUND: The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.METHODS: Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.RESULTS: We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior).CONCLUSIONS: Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.

KW - Behavioral

KW - Genetic correlation

KW - GWAS

KW - Heritability

KW - Psychiatric

KW - Sex differences

UR - http://www.scopus.com/inward/record.url?scp=85102837416&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2020.12.024

DO - 10.1016/j.biopsych.2020.12.024

M3 - Journal article

C2 - 33648717

VL - 89

SP - 1127

EP - 1137

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 12

ER -

ID: 64180851