Birth Weight Predicts Risk of Cardiovascular Disease Within Dizygotic but Not Monozygotic Twin Pairs

Abstract

Background— The widely reported inverse association between birth weight and risk of cardiovascular disease (CVD) has sparked theories about early life determinants of adult disease. Within-twin-pair analysis provides a unique opportunity to investigate whether factors shared within twin pairs influence the association. Methods and Results— In a population-based cohort of like-sexed twins with known zygosity born in Sweden from 1926 to 1958, disease-discordant twin pairs were identified through linkage to the National Inpatient and Cause of Death registers between 1973 and 2006. Co-twin–control analyses were performed on twins discordant for cardiovascular disease (n=3884), coronary heart disease (n=2668), and stroke (n=1372). Overall, inverse associations between birth weight and risk of cardiovascular diseases were seen within dizygotic but not monozygotic twin pairs. In dizygotic twins, the odds ratios for a 1-kg within-pair increase in birth weight were 0.74 (95% confidence interval, 0.56 to 0.98) for coronary heart disease and 0.57 (95% confidence interval, 0.37 to 0.88) for stroke. Conversely, no statistically significant associations were found within monozygotic twins (for coronary heart disease: odds ratio, 1.10; 95% confidence interval, 0.73 to 1.68; for stroke: odds ratio, 0.92; 95% confidence interval, 0.48 to 1.80). Conclusions— We found an association between birth weight and risk of cardiovascular disease within disease-discordant dizygotic but not monozygotic twin pairs. This indicates that the association between birth weight and cardiovascular disease could be a result of common causes, and that factors that vary within dizygotic but not monozygotic twin pairs may help identify them.