Background Inverse correlations have been reported between birth weight and the Metabolic Syndrome (abdominal obesity, insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and hypertension). These correlations are thought to re¯ect primarily nutritional inadequacies during fetal and early life. We explored familial in¯uences on these correlations.
Methods Using birth weight data on 602 subjects from 65 pedigrees, we partitioned phenotypic correlations into familial and non-familial. The former are usually regarded as re¯ecting primarily genetic in¯uences, although they may also re¯ect environmental in¯uences that are shared by family members, and the latter re¯ect random environmental in¯uences.
Results A consistent pattern of positive familial and inverse non-familial correlations were observed. The strongest familial correlations were between birth weight and fasting insulin (r=0.58, p=0.002), leptin (r=0.48, p=0.021), split proinsulin (r=0.51, p=0.090), and heart rate (r=0.39, p=0.037). An inverse familial correlation was observed with HDL cholesterol (r=x0.28, p=0.018). Non-familial correlations were weaker and only two ± subscapular-to-triceps skinfold ratio and fasting insulin ± were statistically signi®cant.
Conclusion
Since the familial and non-familial correlations were in opposite directions, we attribute the former to the pleiotropic effects of genes. Speci®cally, we conclude that genes that increase birth weight also worsen the Metabolic Syndrome in adult life. Since the inverse correlations reported in the literature re¯ect mainly cohorts born in the early part of the 20th century, improved maternal nutrition since then may have allowed the expression of genetic in¯uences in our participants, all of whom were born after 1950.