Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians

Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, in-cluding those in KLF14 (rs4731702), MOB2 (rs2334499), and KCNQ1 (rs2237892, rs231362). We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 iden-tified in previous genome-wide association studies (rs2237895, rs2299620), in 7,351 Pima Indians from 4,549 nuclear families; 34 % of participants had diabetes. In a subset of 287 normoglyce-mic individuals, acute insulin secretion was measured by an in-travenous glucose tolerance test. Statistically significant (P, 0.05) parent-of-origin effects were seen for association with type 2 diabetes for all variants. The strongest effect was seen at rs2299620 in KCNQ1; the C allele was associated with increased diabetes when maternally derived (odds ratio [OR], 1.92; P = 4.1 3 10212), but not when paternally derived (OR, 0.93; P = 0.47; P