Sex differences in brain protein expression and disease

被引：12

作者：

Wingo, Aliza P. ^{[1
,2
]}

Liu, Yue ^{[3
]}

Gerasimov, Ekaterina S. ^{[3
]}

Vattathil, Selina M. ^{[3
]}

Liu, Jiaqi ^{[3
]}

Cutler, David J. ^{[4
]}

Epstein, Michael P. ^{[4
]}

Blokland, Gabriella A. M. ^{[5
]}

Thambisetty, Madhav ^{[6
]}

Troncoso, Juan C. ^{[7
]}

Duong, Duc M. ^{[8
]}

Bennett, David A. ^{[9
]}

Levey, Allan I. ^{[3
,10
]}

Seyfried, Nicholas T. ^{[8
,10
]}

Wingo, Thomas S. ^{[3
,4
,10
]}

机构：

[1] Vet Affairs Atlanta Hlth Care Syst, Decatur, GA 30033 USA

[2] Emory Univ, Dept Psychiat, Sch Med, Atlanta, GA 30307 USA

[3] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30307 USA

[4] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30307 USA

[5] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

[6] Natl Inst Aging, Clin & Translat Neurosci Sect, Lab Behav Neurosci, NIH, Bethesda, MD USA

[7] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA

[8] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA USA

[9] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL USA

[10] Emory Univ, Sch Med, Goizueta Alzheimers Dis Ctr, Atlanta, GA 30307 USA

来源：

NATURE MEDICINE | 2023年 / 29卷 / 9期

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENETIC ARCHITECTURE; ADAPTER PROTEIN; KINASE-A; ASSOCIATION; DISORDERS; MICROGLIA; GALECTIN-3; PATHWAY; STXBP3;

D O I：

10.1038/s41591-023-02509-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Most complex human traits differ by sex, but we have limited insight into the underlying mechanisms. Here, we investigated the influence of biological sex on protein expression and its genetic regulation in 1,277 human brain proteomes. We found that 13.2% (1,354) of brain proteins had sex-differentiated abundance and 1.5% (150) of proteins had sex-biased protein quantitative trait loci (sb-pQTLs). Among genes with sex-biased expression, we found 67% concordance between sex-differentiated protein and transcript levels; however, sex effects on the genetic regulation of expression were more evident at the protein level. Considering 24 psychiatric, neurologic and brain morphologic traits, we found that an average of 25% of their putatively causal genes had sex-differentiated protein abundance and 12 putatively causal proteins had sb-pQTLs. Furthermore, integrating sex-specific pQTLs with sex-stratified genome-wide association studies of six psychiatric and neurologic conditions, we uncovered another 23 proteins contributing to these traits in one sex but not the other. Together, these findings begin to provide insights into mechanisms underlying sex differences in brain protein expression and disease. Analyses of 1,277 human brain proteomes reveal the extent of sex differences in the brain and identify genes associated with neuropsychiatric traits that have differential regulation between males and females.

引用

页码：2224 / 2232

页数：18

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