DOI: 10.1101/208629Oct 25, 2017Paper

Birthweight, Type 2 Diabetes and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian randomization

BioRxiv : the Preprint Server for Biology
Daniela ZanettiErik Ingelsson


Background: Low birthweight (BW) has been associated with a higher risk of hypertension, type 2 diabetes (T2D) and cardiovascular disease (CVD) in epidemiological studies. The Barker hypothesis posits that intrauterine growth restriction resulting in lower BW is causal for these diseases, but causality and mechanisms are difficult to infer from observational studies. Mendelian randomization (MR) is a new tool to address this important question. Methods: We performed regression analyses to assess associations of self-reported BW with CVD and T2D in 237,631 individuals from the UK Biobank, a large population-based cohort study aged 40-69 years recruited across UK in 2006-2010. Further, we assessed the causal relationship of such associations using the two-sample MR approach, estimating the causal effect by contrasting the SNP effects on the exposure with the SNP effects on the outcome using independent publicly available genome-wide association datasets. Results: In the observational analyses, BW showed strong inverse associations with systolic and diastolic blood pressure (β, -0.83 and -0.26; per raw unit in outcomes and SD change in BW; 95% CI, -0.90, -0.75 and -0.31, -0.22, respectively), T2D (odds ratio [OR], 0.83; 95% CI, 0....Continue Reading

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