In contrast, the risk allele rs4311394-G at ARL15, which was associated with lower adiponectin levels, was also associated with: an increased risk of CHD in a consortium of 7 CHD cohorts (Odds ratio [OR] = 1.12, [95% Confidence Interval [CI]: 1.06, 1.17], P = 8.5×10−6, n = 22,421); an increased risk of T2D in the DIAGRAM consortium [15] (OR = 1.11 [95% CI: 1.03, 1.18], P = 3.2×10−3, n = 10,128); and higher glycated hemoglobin in the European Prospective Investigation of Cancer-Norfolk (EPIC-Norfolk) cohort (0.025% per G allele [95% CI: 0.01, 0.04], P = 5.0×10−4, n = 14,168) (Table 3). In the MAGIC consortium [16], the rs4311394-G allele was associated with increased levels of fasting insulin (P = 2.3×10−3, n = 24,614), and demonstrated non-significant trends towards higher HOMA-IR (P = 0.01, n = 24,188) and HOMA-B (P = 0.02, n = 24,130) (Table 4). In the GIANT consortium [17], the same allele demonstrated a modest and non-significant association with decreased BMI (P = 0.016, n = 32,527) (Table S4), indicating that the disease and metabolic trait associations of rs4311394-G are unlikely to be mediated through an increase in BMI.
