Biomaterial Database

Sex differences in brain protein expression and disease. 2023

Aliza P Wingo, and Yue Liu, and Ekaterina S Gerasimov, and Selina M Vattathil, and Jiaqi Liu, and David J Cutler, and Michael P Epstein, and Gabriëlla A M Blokland, and Madhav Thambisetty, and Juan C Troncoso, and Duc M Duong, and David A Bennett, and Allan I Levey, and Nicholas T Seyfried, and Thomas S Wingo

Veterans Affairs Atlanta Health Care System, Decatur, GA, USA. aliza.wingo@emory.edu.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012727	Sex Characteristics	Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.	Gender Characteristics,Gender Differences,Gender Dimorphism,Sex Differences,Sex Dimorphism,Sexual Dichromatism,Sexual Dimorphism,Characteristic, Gender,Characteristic, Sex,Dichromatism, Sexual,Dichromatisms, Sexual,Difference, Sex,Dimorphism, Gender,Dimorphism, Sex,Dimorphism, Sexual,Gender Characteristic,Gender Difference,Gender Dimorphisms,Sex Characteristic,Sex Difference,Sex Dimorphisms,Sexual Dichromatisms,Sexual Dimorphisms
D055106	Genome-Wide Association Study	An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers to identify gene candidates or quantitative trait loci associated with a specific organism trait or specific disease or condition.	Genome Wide Association Analysis,Genome Wide Association Study,GWA Study,Genome Wide Association Scan,Genome Wide Association Studies,Whole Genome Association Analysis,Whole Genome Association Study,Association Studies, Genome-Wide,Association Study, Genome-Wide,GWA Studies,Genome-Wide Association Studies,Studies, GWA,Studies, Genome-Wide Association,Study, GWA,Study, Genome-Wide Association
D020412	Multifactorial Inheritance	A pattern of inheritance of a trait that includes the contributions from more than one gene.	Oligogenic Inheritance,Polygenic Inheritance,Polygenic Traits,Complex Inheritance,Complex Traits,Multigenic Inheritance,Multigenic Traits,Oligogenic Traits,Polygenic Characters,Character, Polygenic,Characters, Polygenic,Complex Trait,Inheritance, Complex,Inheritance, Multifactorial,Inheritance, Multigenic,Inheritance, Oligogenic,Inheritance, Polygenic,Multigenic Trait,Oligogenic Trait,Polygenic Character,Polygenic Trait,Trait, Complex,Trait, Multigenic,Trait, Oligogenic,Trait, Polygenic,Traits, Complex,Traits, Multigenic,Traits, Oligogenic,Traits, Polygenic