Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes.
Diabetologia
; 59(8): 1702-13, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27155871
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 p POE = 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 p POE = 0.01; HTB p POE = 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Proteínas de Neoplasias
Límite:
Adult
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Female
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Humans
/
Middle aged
Idioma:
En
Revista:
Diabetologia
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suecia