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Diabetologia

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23.06.2016 | Article

Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study

verfasst von: Tiange Wang, Tao Huang, Yanping Li, Yan Zheng, JoAnn E. Manson, Frank B. Hu, Lu Qi

Erschienen in: Diabetologia | Ausgabe 9/2016

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Abstract

Aims/hypothesis

Low birthweight has been associated with a high risk of type 2 diabetes mellitus in observational studies. However, it remains unclear whether this relation is causal.

Methods

The present study included 3627 individuals with type 2 diabetes and 12,974 control participants of European ancestry from the Nurses’ Health Study and the Health Professionals Follow-Up Study. A genetic risk score (GRS) was calculated based on five low-birthweight-related single nucleotide polymorphisms (SNPs). We assessed the evidence for causality first by examining the association of the GRS and the individual SNPs with type 2 diabetes, and second by performing a Mendelian randomisation analysis to estimate the potentially causal effect size of low birthweight on type 2 diabetes.

Results

In a meta-analysis of the two studies, each 1 point increment in the GRS was associated with a 6% (95% CI 3%, 9%) higher risk of type 2 diabetes. CCNL1 rs900400 and 5q11.2 rs4432842 showed dose–response associations with risk of type 2 diabetes; the corresponding ORs and 95% CIs were 1.09 (1.03, 1.16) and 1.09 (1.02, 1.16), respectively. Furthermore, we observed an overall Mendelian randomisation OR of 2.94 (95% CI 1.70, 5.16; p < 0.001) for type 2 diabetes per 1 SD lower genetically determined birthweight.

Conclusions/interpretation

A genetically lowered birthweight was associated with increased susceptibility to type 2 diabetes. Our findings support a potential causal relation between birthweight and risk of type 2 diabetes, providing new evidence to support the role of intrauterine exposures in the pathogenesis of type 2 diabetes.

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Titel: Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study
verfasst von: Tiange Wang
Tao Huang
Yanping Li
Yan Zheng
JoAnn E. Manson
Frank B. Hu
Lu Qi
Publikationsdatum: 23.06.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 9/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4019-z

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Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study

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