Birth weight and risk of ischemic heart disease: A Mendelian randomization study

Low birth weight is a risk factor for cardiovascular disease. However, the association could be confounded by many factors. We used Mendelian randomization to clarify the role of birth weight in ischemic heart disease (IHD) and lipids. We used all 7 single nucleotide polymorphisms (SNPs) independently contributing to birth weight at genome wide significance (p < 5 × 10^-8) in separate sample instrumental variable analysis to estimate the effect of birth weight on IHD using the CARDIoGRAMplusC4D 1000 Genomes based GWAS case (n = 60,801)-control (n = 123,504) study and on lipids using GLGC (n = 188,577). Higher genetically predicted birth weight was associated with lower risk of IHD (odds ratio (OR) 0.96 per 100 grams, 95% confidence interval (CI) 0.93 to 0.99), but the association was not robust to sensitivity analyses excluding SNPs related to height or use of weighted median methods. Genetically predicted birth weight was not associated with low density lipoprotein cholesterol or triglycerides, but was associated with lower high density lipoprotein cholesterol (-0.014 standard deviation, 95% CI -0.027 to -0.0005) and the association was more robust to the sensitivity analyses. Our study does not show strong evidence for an effect of birth weight on IHD and lipids.