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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09

AUTHORS

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

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. More... »

PAGES

1920-1927

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-016-4019-z

DOI

http://dx.doi.org/10.1007/s00125-016-4019-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031098292

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27333884


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