Diabetologia: A genome-wide crossover trait analysis identifies shared loci and causal associations between type 2 diabetes and glycemic traits and polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age

Observed associations between two traits often indicate shared environmental exposures and shared genetic components, as genetic variation either has independent effects on the two traits (horizontal pleiotropy or pleiotropy) or through their effect on the other The effect of a trait to affect a trait (vertical pleiotropy or causality)

Objectives: In the current study, we aimed to investigate type 2 diabetes, glycemic traits and independence of body mass by performing a comprehensive genetic analysis using the largest genome-wide association study (GWAS) summary statistics for each trait to date Exponential shared genetic contributions among PCOS

Methods: Using summary statistics from the largest genome-wide association study to date for type 2 diabetes, type 2 diabetes, body mass index (T2DMadjBMI), fasting glucose, fasting insulin, 2h post-dose glucose (all for body mass) index), HbA1c, and PCOS were adjusted for all studies in populations of European ancestry

RESULTS: Type 2 diabetes and PCOS were positively correlated overall, mainly influenced by body mass index (rg=0.

Table 1 Genome-wide genetic associations between type 2 diabetes/glycemia traits and PCOS

Table 2 Cross-trait meta-analysis of type 2 diabetes/glycemia traits and PCOS

Table 3 Significant genes shared between type 2 diabetes/glycemia traits and PCOS identified from TWAS using gene expression across 48 GTEx tissues

Figure 1.

Conclusions: We identified potential genetic associations of type 2 diabetes, glycemic signatures, and PCOS, driven by pleiotropy and causal mediators, some of which were independent of body mass index

Original source: Liu Q, Tang B, Zhu Z, et al.