Birth weight predicts risk of cardiovascular disease within dizygotic but not monozygotic twin pairs: a large population-based co-twin-control study.

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.