RT Journal Article
SR Electronic
T1 The role of gene expression on human sexual dimorphism: too early to call
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.15.042986
DO 10.1101/2020.04.15.042986
A1 Porcu, Eleonora
A1 Claringbould, Annique
A1 Lepik, Kaido
A1 ,
A1 Richardson, Tom G.
A1 Santoni, Federico A.
A1 Franke, Lude
A1 Reymond, Alexandre
A1 Kutalik, Zoltán
YR 2020
UL http://biorxiv.org/content/early/2020/04/17/2020.04.15.042986.abstract
AB The genetic underpinning of sexual dimorphism is very poorly understood. The prevalence of many diseases differs between men and women, which could be in part caused by sex-specific genetic effects. Nevertheless, only a few published genome-wide association studies (GWAS) were performed separately in each sex. The reported enrichment of expression quantitative trait loci (eQTLs) among GWAS–associated SNPs suggests a potential role of sex-specific eQTLs in the sex-specific genetic mechanism underlying complex traits.To explore this scenario, we performed a genome-wide analysis of sex-specific whole blood RNA-seq eQTLs from 3,447 individuals. Among 9 million SNP-gene pairs showing sex-combined associations, we found 18 genes with significant sex-specific cis-eQTLs (FDR 5%). Our phenome-wide association study of the 18 top sex-specific eQTLs on >700 traits unraveled that these eQTLs do not systematically translate into detectable sex-specific trait-associations. Power analyses using real eQTL- and causal effect sizes showed that millions of samples would be necessary to observe sex-specific trait associations that are fully driven by sex-specific cis-eQTLs. Compensatory effects may further hamper their detection. In line with this observation, we confirmed that the sex-specific trait-associations detected so far are not driven by sex-specific cis-eQTLs.Competing Interest StatementThe authors have declared no competing interest.