Fig. 1: Sex-differentiated genetic effect exists in genome-wide and in near-DMET gene regions for complex traits. | Nature Communications

Fig. 1: Sex-differentiated genetic effect exists in genome-wide and in near-DMET gene regions for complex traits.

From: Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes

Fig. 1

a Overview of trait selection and analytical pipeline. We defined each cis-DMET gene region as ±1 Mb from the DMET gene transcription start site. We first selected available human complex traits for which sex-stratified GWAS summary statistics are available17. The trait list was further narrowed down by the presence of significant SNP-trait associated with the DMET gene regions. In total, we evaluated 564 traits (421 categorical/binary traits and 143 non-binary/non-categorical traits). We then performed several sex-aware analyses (sex-stratified heritability, male-female genetic correlation, sex-differentiated genetic effects) to characterize sex differences both a genome-wide and in DMET gene regions. Lastly, we performed sex-stratified colocalization analysis between sexes to identify DMET variants’ unique SNP-traits association in each sex for the traits that demonstrated sex differences in genetic basis. b Male and female heritability estimates for 564 traits. Each point represents the estimated heritability for a given trait. Blue indicates the 83 traits with a significant (FDR < 0.05) sex difference in heritability. c Number of sex-differentiated effects (SDEs) mapping to DMET genes regions. d 15 overlapped traits with SDEs in cis-DMET gene regions and a significant sex difference in heritability. e Sex-stratified colocalization of GWAS signal for 8 traits. SDEs are labeled on the x-axis, and the traits are labeled on the y-axis. The posterior probability of hypothesis (PPH) 1 (blue, representing SNP putatively causal only in Male) and 2 (red, representing SNP putatively causal only in Female) are color-labeled and the value of PPH is represented by the size of the circle; only PPH > 0.25 is shown. The variant effect and Combined Annotation Dependent Depletion (CADD) score are shown for each SNP. The asterisk indicates self-reported traits. f LocusZoom plots of SLC22A12 (left) and SLC66A1 (right) from sex-stratified GWAS for self-reported gout and self-reported hypothyroidism, respectively. Linkage disequilibrium (LD) between variants is quantified by the squared Pearson coefficient of correlation (r2).

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