Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits.
Access full-text PDFOpen Access
Check access options
Check access options
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Khramtsova, Ekaterina A
Goleva, Slavina B
Blokland, Gabriëlla A M
Walters, Raymond K
Coleman, Jonathan R I
Børglum, Anders D
Bulik, Cynthia M
Lee, Phil H
Mathews, Carol A
Peterson, Roseann E
Winham, Stacey J
Edenberg, Howard J
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
Journal titleBiological psychiatry
Publication Begin page1127
Publication End page1137
MetadataShow full item record
AbstractThe 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.
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 (r < 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.
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).
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.
CitationMartin 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. Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits. Biol Psychiatry. 2021 Jun 15;89(12):1127-1137. doi: 10.1016/j.biopsych.2020.12.024. Epub 2021 Jan 9. PMID: 33648717; PMCID: PMC8163257.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
- The shared genetic architecture between epidemiological and behavioral traits with lung cancer.
- Authors: Pettit RW, Byun J, Han Y, Ostrom QT, Edelson J, Walsh KM, Bondy ML, Hung RJ, McKay JD, Amos CI
- Issue date: 2021 Sep 2
- Variable prediction accuracy of polygenic scores within an ancestry group.
- Authors: Mostafavi H, Harpak A, Agarwal I, Conley D, Pritchard JK, Przeworski M
- Issue date: 2020 Jan 30
- Contrasting the Genetic Architecture of 30 Complex Traits from Summary Association Data.
- Authors: Shi H, Kichaev G, Pasaniuc B
- Issue date: 2016 Jul 7
- Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents.
- Authors: Docherty AR, Shabalin AA, DiBlasi E, Monson E, Mullins N, Adkins DE, Bacanu SA, Bakian AV, Crowell S, Chen D, Darlington TM, Callor WB, Christensen ED, Gray D, Keeshin B, Klein M, Anderson JS, Jerominski L, Hayward C, Porteous DJ, McIntosh A, Li Q, Coon H
- Issue date: 2020 Oct 1
- Characterizing the effect of background selection on the polygenicity of brain-related traits.
- Authors: Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R
- Issue date: 2021 Jan