Fig. 5. Clinical implications of genetic variation at the SRD5A2 locus.

a, Stacked regional association plots for eight steroid metabolites, the risk of male-pattern baldness and depression in a 2-Mb window around the most likely causal gene, SRD5A2. Association statistics (P values from linear mixed models) for levels of plasma metabolites were derived from linear regression models as described in the text, and summary statistics for male-pattern baldness and depression were extracted from the literature^17,19. The two-color gradients indicate the LD (r²) with the candidate causal variants identified using multi-trait colocalization: rs112881196 (blue, lead signal for male-pattern baldness) and rs62142080 (orange, lead signal for depression). b, Forest plot showing effect estimates (box) and 95% confidence intervals for rs112881196 (top panel) and rs62142080 (lower panel) across all traits considered. Effects for depression are given as odds ratios, because logistic regression models were used for association testing, whereas effects for all other traits were estimated using linear regression models. Effect estimates and corresponding standard errors for male-pattern baldness and depression were obtained from the same studies as described in the text. Sample sizes for metabolites are described in Supplementary Table 8. Open symbols indicate non-significant effects (P > 0.05). c, Scheme describing the putative mechanism by which the two genetic variants nearby SRD5A2 alter steroid metabolism. Lower plasma levels of metabolites downstream of 5α-reduction of androgenic steroids but higher levels of the main 5β-reduced androgen metabolite etiocholanolone indicate lower activity of steroid 5α-reductase 2 (SRD5A2) conferred by variants associated with a lower risk for male-pattern baldness (via rs112881196) but increased risk for depression (via rs62142080). Parts of this figure were created with BioRender.com.