Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits

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Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. / Martin, Joanna; Khramtsova, Ekaterina A.; Goleva, Slavina B.; Blokland, Gabriëlla A.M.; Traglia, Michela; Walters, Raymond K.; Hübel, Christopher; Coleman, Jonathan R.I.; Breen, Gerome; Børglum, Anders D.; Demontis, Ditte; Grove, Jakob; Werge, Thomas; Bralten, Janita; Bulik, Cynthia M.; Lee, Phil H.; Mathews, Carol A.; Peterson, Roseann E.; Winham, Stacey J.; Wray, Naomi; Edenberg, Howard J.; Guo, Wei; Yao, Yin; Neale, Benjamin M.; Faraone, Stephen V.; Petryshen, Tracey L.; Weiss, Lauren A.; Duncan, Laramie E.; Goldstein, Jill M.; Smoller, Jordan W.; Stranger, Barbara E.; Davis, Lea K.; Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium.

In: Biological Psychiatry, Vol. 89, No. 12, 2021, p. 1127-1137.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Martin, J, Khramtsova, EA, Goleva, SB, Blokland, GAM, Traglia, M, Walters, RK, Hübel, C, Coleman, JRI, Breen, G, Børglum, AD, Demontis, D, Grove, J, Werge, T, Bralten, J, Bulik, CM, Lee, PH, Mathews, CA, Peterson, RE, Winham, SJ, Wray, N, Edenberg, HJ, Guo, W, Yao, Y, Neale, BM, Faraone, SV, Petryshen, TL, Weiss, LA, Duncan, LE, Goldstein, JM, Smoller, JW, Stranger, BE, Davis, LK & 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

Martin, J., Khramtsova, E. A., Goleva, S. B., Blokland, G. A. M., Traglia, M., Walters, R. K., Hübel, C., Coleman, J. R. I., Breen, G., Børglum, A. D., Demontis, D., Grove, J., Werge, T., Bralten, J., Bulik, C. M., Lee, P. H., Mathews, C. A., Peterson, R. E., Winham, S. J., ... 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

Vancouver

Martin J, Khramtsova EA, Goleva SB, Blokland GAM, Traglia M, Walters RK et al. 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

Author

Martin, Joanna ; Khramtsova, Ekaterina A. ; Goleva, Slavina B. ; Blokland, Gabriëlla A.M. ; Traglia, Michela ; Walters, Raymond K. ; Hübel, Christopher ; Coleman, Jonathan R.I. ; Breen, Gerome ; Børglum, Anders D. ; Demontis, Ditte ; Grove, Jakob ; Werge, Thomas ; Bralten, Janita ; Bulik, Cynthia M. ; Lee, Phil H. ; Mathews, Carol A. ; Peterson, Roseann E. ; Winham, Stacey J. ; Wray, Naomi ; Edenberg, Howard J. ; Guo, Wei ; Yao, Yin ; Neale, Benjamin M. ; Faraone, Stephen V. ; Petryshen, Tracey L. ; Weiss, Lauren A. ; Duncan, Laramie E. ; Goldstein, Jill M. ; Smoller, Jordan W. ; Stranger, Barbara E. ; Davis, Lea K. ; 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{0a323edd188c4c4ea8c03d7e3770d31c,
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 Martin Alda and Marco Bortolato and Burton, {Christie L.} and Enda Byrne and Carey, {Caitlin E.} and Lauren Erdman and Huckins, {Laura M.} and Manuel Mattheisen and Elise Robinson and Eli Stahl and {Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium}",
note = "Publisher Copyright: {\textcopyright} 2021 Society of Biological Psychiatry",
year = "2021",
doi = "10.1016/j.biopsych.2020.12.024",
language = "English",
volume = "89",
pages = "1127--1137",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier",
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 - Alda, Martin

AU - Bortolato, Marco

AU - Burton, Christie L.

AU - Byrne, Enda

AU - Carey, Caitlin E.

AU - Erdman, Lauren

AU - Huckins, Laura M.

AU - Mattheisen, Manuel

AU - Robinson, Elise

AU - Stahl, Eli

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

N1 - Publisher Copyright: © 2021 Society of Biological Psychiatry

PY - 2021

Y1 - 2021

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

U2 - 10.1016/j.biopsych.2020.12.024

DO - 10.1016/j.biopsych.2020.12.024

M3 - Journal article

C2 - 33648717

AN - SCOPUS:85102837416

VL - 89

SP - 1127

EP - 1137

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 12

ER -

ID: 272237822