Matches in SemOpenAlex for { <https://semopenalex.org/work/W4315786011> ?p ?o ?g. }
- W4315786011 abstract "Sex differences have been widely observed in human health. However, little is known about the underlying mechanism behind these observed sex differences. We hypothesize that sex-differentiated genetic effects are contributors of these phenotypic differences. Focusing on a collection of drug metabolism enzymes and transporters (DMET) genes, we discover sex-differentiated genetic regulatory mechanisms between these genes and human complex traits. Here, we show that sex-differentiated genetic effects were present at genome-level and at DMET gene regions for many human complex traits. These sex-differentiated regulatory mechanisms are reflected in the levels of gene expression and endogenous serum biomarkers. Through Mendelian Randomization analysis, we identify putative sex-differentiated causal effects in each sex separately. Furthermore, we identify and validate sex differential gene expression of a subset of DMET genes in human liver samples. We observe higher protein abundance and enzyme activity of CYP1A2 in male-derived liver microsomes, which leads to higher level of an active metabolite formation of clozapine, a commonly prescribed antipsychotic drug. Taken together, our results demonstrate the presence of sex-differentiated genetic effects on DMET gene regulation, which manifest in various phenotypic traits including disease risks and drug responses." @default.
- W4315786011 created "2023-01-13" @default.
- W4315786011 creator A5001175433 @default.
- W4315786011 creator A5010839205 @default.
- W4315786011 creator A5020575990 @default.
- W4315786011 creator A5022923234 @default.
- W4315786011 creator A5030681379 @default.
- W4315786011 creator A5064521172 @default.
- W4315786011 creator A5090067435 @default.
- W4315786011 date "2023-01-12" @default.
- W4315786011 modified "2023-10-16" @default.
- W4315786011 title "Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes" @default.
- W4315786011 cites W1543017846 @default.
- W4315786011 cites W1803760021 @default.
- W4315786011 cites W1968953959 @default.
- W4315786011 cites W1969692023 @default.
- W4315786011 cites W1973237138 @default.
- W4315786011 cites W1990335454 @default.
- W4315786011 cites W2000810545 @default.
- W4315786011 cites W2014169080 @default.
- W4315786011 cites W2034091689 @default.
- W4315786011 cites W2036613552 @default.
- W4315786011 cites W2040134200 @default.
- W4315786011 cites W2040735587 @default.
- W4315786011 cites W2043168039 @default.
- W4315786011 cites W2053399504 @default.
- W4315786011 cites W2056475446 @default.
- W4315786011 cites W2073895192 @default.
- W4315786011 cites W2074107757 @default.
- W4315786011 cites W2075225853 @default.
- W4315786011 cites W2081308931 @default.
- W4315786011 cites W2097174145 @default.
- W4315786011 cites W2118247434 @default.
- W4315786011 cites W2140742732 @default.
- W4315786011 cites W2143121451 @default.
- W4315786011 cites W2145931128 @default.
- W4315786011 cites W2152000559 @default.
- W4315786011 cites W2155882052 @default.
- W4315786011 cites W2169085718 @default.
- W4315786011 cites W2170146596 @default.
- W4315786011 cites W2179438025 @default.
- W4315786011 cites W2185216198 @default.
- W4315786011 cites W2277720126 @default.
- W4315786011 cites W2326963943 @default.
- W4315786011 cites W2494789486 @default.
- W4315786011 cites W2619267000 @default.
- W4315786011 cites W2751073462 @default.
- W4315786011 cites W2765789483 @default.
- W4315786011 cites W2804772768 @default.
- W4315786011 cites W2805983714 @default.
- W4315786011 cites W2806581773 @default.
- W4315786011 cites W2895486342 @default.
- W4315786011 cites W2901578726 @default.
- W4315786011 cites W2906199739 @default.
- W4315786011 cites W2914198126 @default.
- W4315786011 cites W2950099124 @default.
- W4315786011 cites W2950885009 @default.
- W4315786011 cites W2990689160 @default.
- W4315786011 cites W3004892753 @default.
- W4315786011 cites W3007352713 @default.
- W4315786011 cites W3012400425 @default.
- W4315786011 cites W3021797386 @default.
- W4315786011 cites W3037588075 @default.
- W4315786011 cites W3044725283 @default.
- W4315786011 cites W3057302762 @default.
- W4315786011 cites W3084331777 @default.
- W4315786011 cites W3118256013 @default.
- W4315786011 cites W3121239749 @default.
- W4315786011 cites W3129948148 @default.
- W4315786011 cites W3133859624 @default.
- W4315786011 cites W3153178523 @default.
- W4315786011 cites W3160579173 @default.
- W4315786011 cites W3161254945 @default.
- W4315786011 cites W3162800482 @default.
- W4315786011 cites W3175801695 @default.
- W4315786011 cites W3198822349 @default.
- W4315786011 cites W3200841924 @default.
- W4315786011 cites W3202212354 @default.
- W4315786011 doi "https://doi.org/10.1038/s41467-023-35808-6" @default.
- W4315786011 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36635277" @default.
- W4315786011 hasPublicationYear "2023" @default.
- W4315786011 type Work @default.
- W4315786011 citedByCount "7" @default.
- W4315786011 countsByYear W43157860112023 @default.
- W4315786011 crossrefType "journal-article" @default.
- W4315786011 hasAuthorship W4315786011A5001175433 @default.
- W4315786011 hasAuthorship W4315786011A5010839205 @default.
- W4315786011 hasAuthorship W4315786011A5020575990 @default.
- W4315786011 hasAuthorship W4315786011A5022923234 @default.
- W4315786011 hasAuthorship W4315786011A5030681379 @default.
- W4315786011 hasAuthorship W4315786011A5064521172 @default.
- W4315786011 hasAuthorship W4315786011A5090067435 @default.
- W4315786011 hasBestOaLocation W43157860111 @default.
- W4315786011 hasConcept C104317684 @default.
- W4315786011 hasConcept C106208931 @default.
- W4315786011 hasConcept C111472728 @default.
- W4315786011 hasConcept C127716648 @default.
- W4315786011 hasConcept C135763542 @default.
- W4315786011 hasConcept C138885662 @default.
- W4315786011 hasConcept C150194340 @default.