Details

Autor(en) / Beteiligte

• 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.
• Alda, Martin
• Bortolato, Marco
• Burton, Christie L.
• Byrne, Enda
• Carey, Caitlin E.
• Erdman, Lauren
• Huckins, Laura M.
• Mattheisen, Manuel
• Robinson, Elise
• Stahl, Eli

Titel

Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits

Ist Teil von

• Biological psychiatry (1969), 2021-06, Vol.89 (12), p.1127-1137

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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.