Strong parent-of-Origin effects in the association of kcnq1 variants with type 2 diabetes in american indians

Robert L. Hanson, Tingwei Guo, Yunhua L. Muller, Jamie Fleming, William C. Knowler, Sayuko Kobes, Clifton Bogardus, Leslie J. Baier

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Abstract

Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including 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 identified 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 normoglycemic individuals, acute insulin secretion was measured by an intravenousglucose 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 × 10-12), but not when paternally derived (OR, 0.93; P = 0.47; P = 9.9 × 10 -6 for difference in maternal and paternal effects). A maternally derived C allele also was associated with a 28% decrease in insulin secretion (P = 0.002). This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2, and KCNQ1. In Pima Indians, the effect of maternally derived KCNQ1 variants appears to be mediated through decreased insulin secretion and is particularly strong, accounting for 4% of the variance in liability to diabetes.

Original languageEnglish (US)
Pages (from-to)2984-2991
Number of pages8
JournalDiabetes
Volume62
Issue number8
DOIs
StatePublished - Aug 1 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hanson, R. L., Guo, T., Muller, Y. L., Fleming, J., Knowler, W. C., Kobes, S., Bogardus, C., & Baier, L. J. (2013). Strong parent-of-Origin effects in the association of kcnq1 variants with type 2 diabetes in american indians. Diabetes, 62(8), 2984-2991. https://doi.org/10.2337/db12-1767