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Heritability of Childhood Weight Gain from Birth and Risk Markers for Adult Metabolic Disease in Prepubertal Twins

Department of Paediatrics (K.B., K.K.O., D.B.D.), University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom; Medical Research Council Epidemiology Unit (K.K.O., J.H.Z.), Institute of Metabolic Science, Cambridge CB2 0QQ, United Kingdom; Department of Paediatrics (N.M.), Rotunda Hospital, Dublin 1, Ireland; Department of Paediatrics (M.L.A.), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; and Research Center for Exercise and Health (M.W.P.), Department of Biomedical Kinesiology, Katholieke Universiteit Leuven, B-3001 Leuven, Belgium

Address all correspondence and requests for reprints to: Professor David Dunger, Department of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Box 116, Cambridge CB2 0QQ, United Kingdom. E-mail: dbd25{at}cam.ac.uk.

Objective: Associations between size at birth, postnatal weight gain, and potential risk for adult disease have been variably explained by in utero exposures or genetic risk that could affect both outcomes. We utilized a twin model to explore these hypotheses.

Methods: One hundred pairs of healthy twins aged 8.9 yr (range, 7.2–10.9 yr) had fasting blood samples collected, blood pressure (BP) measured, and anthropometry assessed. All measurements were converted to SD scores (SDS) to adjust for age and sex.

Results: Mean birth weights in both monozygotic and dizygotic twins were –0.90 SDS lower than the UK reference. In postnatal life, 58% of monozygotic twins and 59% of dizygotic twins showed rapid weight gain (a change of more than +0.67 in weight SDS) from birth. Postnatal weight gain was positively associated with sum of skinfolds (r = 0.51; P < 0.0005), fasting insulin levels (r = 0.35; P < 0.0005), systolic BP (r = 0.30; P < 0.0005), and diastolic BP (r = 0.15; P < 0.05) at follow-up. Heritability estimates (additive genetic components) were calculated using variance components models for: birth weight, 44%; postnatal weight gain, 80%; childhood height, 89%; body mass index, 72%; sum of skinfolds, 89%; waist circumference, 74%; fasting insulin, 65%; systolic BP, 33%; and diastolic BP, 29%.

Conclusions: Postnatal weight gain from birth, rather than birth weight, was associated with childhood risk markers for adult metabolic disease. Childhood weight gain was highly heritable, and genetic factors associated with postnatal weight gain are likely to also contribute to risks for adult disease.