Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes

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Bibtex

@article{c1025a0642c04a279d3195f6714973a4,
title = "Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes",
abstract = "Aims/hypothesis: Genome-wide association studies (GWAS) have identified more than 65 genetic loci associated with risk of type 2 diabetes. However, the contribution of distorted parental transmission of alleles to risk of type 2 diabetes has been mostly unexplored. Our goal was therefore to search for parent-of-origin effects (POE) among type 2 diabetes loci in families. Methods: Families from the Botnia study (n = 4,211, 1,083 families) were genotyped for 72 single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes and assessed for POE on type 2 diabetes. The family-based Hungarian Transdanubian Biobank (HTB) (n = 1,463, >135 families) was used to replicate SNPs showing POE. Association of type 2 diabetes loci within families was also tested. Results: Three loci showed nominal POE, including the previously reported variants in KCNQ1, for type 2 diabetes in families from Botnia (rs2237895: pPOE = 0.037), which can be considered positive controls. The strongest POE was seen for rs7578597 SNP in the THADA gene, showing excess transmission of the maternal risk allele T to diabetic offspring (Botnia: pPOE = 0.01; HTB pPOE = 0.045). These data are consistent with previous evidence of allelic imbalance for expression in islets, suggesting that the THADA gene can be imprinted in a POE-specific fashion. Five CpG sites, including those flanking rs7578597, showed differential methylation between diabetic and non-diabetic donor islets. Conclusions/interpretation: Taken together, the data emphasise the need for genetic studies to consider from which parent an offspring has inherited a susceptibility allele.",
keywords = "Families, Genetic association studies, KCNQ1, Maternal effects, Methylation, Parent-of-origin, Parental transmission, THADA, Type 2 diabetes",
author = "Prasad, {Rashmi B.} and Anna Lessmark and Peter Almgren and Gy{\"o}rgyi Kovacs and Ola Hansson and Nikolay Oskolkov and Marta Vitai and Claes Ladenvall and Peter Kovacs and Joao Fadista and Michael Lachmann and Yuedan Zhou and Emily Sonestedt and Wenny Poon and Wollheim, {Claes B.} and Marju Orho-Melander and Michael Stumvoll and Tiinamaija Tuomi and Svante P{\"a}{\"a}bo and Laszlo Koranyi and Leif Groop",
year = "2016",
month = "8",
doi = "10.1007/s00125-016-3973-9",
language = "English",
volume = "59",
pages = "1702--1713",
journal = "Diabetologia",
issn = "1432-0428",
publisher = "Springer",
number = "8",

}