For the novel proposed CDKAL1 rs10946398 association, additional data were recently published from deCODE and affiliated investigators in Nature Genetics [21] who proposed a different polymorphism in the same gene (rs7756992) as a T2D marker. The r2 for these two markers was only 0.67 in Caucasians, but 4 other CDKLA1 polymorphisms in the deCODE data [21] have r2 = 1 with rs10946398. Including the deCODE data for the nearest one (rs7774594) in the meta-analysis calculations, the summary odds ratio became 1.13 (95% CI, 1.08–1.18) with p = 2.2×10−7. Moderate between-study heterogeneity persisted (I2 = 43%). In the deCODE presented results for rs7756992 (ref. 13), we estimated very large between-population heterogeneity in the genetic effects between three different racial descent populations (I2 = 76%). Compared with Caucasians, the correlation between rs10946398 (or rs7774594) and rs7756992 was much weaker in Africans (r2 = 0.35). In Africans, deCODE investigators noticed that rs7756992 showed no association effect (odds ratio 1.02). The very large heterogeneity in genetic effects for rs7756992 and the moderate heterogeneity for rs10946398 might suggest that neither polymorphism is the true culprit; the culprit may be more consistently correlated (even in Africans) with rs10946398 than with rs7756992.
