McNeill G, Tuya C, Smith WC: The role of genetic and environmental factors in the association between birthweight and blood pressure: Evidence from meta-analysis of twin studies

College of Medicine and Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
International Journal of Epidemiology (Impact Factor: 9.18). 11/2004; 33(5):995-1001. DOI: 10.1093/ije/dyh260
Source: PubMed


An inverse association between birthweight and later blood pressure has been found in many studies in singletons. Twin studies have been used to examine whether genetic factors or family environment could account for this association.
A systematic review identified 10 studies covering 3901 twin pairs. Meta-analysis of regression coefficients for the association between birthweight and systolic blood pressure was carried out for unpaired versus paired associations and for paired associations in dizygotic versus monozygotic pairs.
After adjustment for current weight or body mass index (BMI), the difference in systolic blood pressure per kg birthweight was -2.0 (95% CI: -3.2, -0.8) mmHg in the unpaired analysis and -0.4 (95% CI: -1.5, 0.7) mmHg in the paired analysis in the same subjects. In the paired analysis by zygosity, in all twins the coefficients were -0.7 (95% CI: -2.3, 0.8) mmHg in dizygotic pairs and -0.8 (95% CI: -2.1, 0.4) mmHg in monozygotic pairs, but in studies which included zygosity tests the coefficients were -1.0 (95% CI: -3.3, 1.6) mmHg in dizygotic pairs and -0.4 (95% CI: -1.9, 1.3) mmHg in monozygotic pairs.
The attenuation of the regression coefficient in the paired analysis provides support for the possibility that factors shared by twins contribute to the association between birthweight and blood pressure in singletons. Comparison of paired analysis in monozygotic and dizygotic pairs could not provide conclusive evidence for a role for genetic as opposed to shared environmental factors.

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Available from: William Cairns S Smith, Nov 14, 2015
    • "Although MZ twins do not necessarily share the same in utero environment, they are more closely matched than unrelated individuals, and they offer a unique opportunity to study the link between early life factors and adult life health. Birth weight discordance in twins may arise through mechanisms not experienced by singletons (Lopriore et al., 2003), but shared results linking birth weight to cardiovascular health are identified in both twins and singletons (McNeill et al., 2004). A recent longitudinal study in twins from birth to 18 months explored genomewide DNA methylation patterns in buccal epithelium (Martino et al., 2013). "
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    ABSTRACT: Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10-8), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.
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    • "It may take large-scale wholegenome screening approaches, as currently underway in the Hap Map project, to ultimately define the relative role of genetic factors for blood pressure distribution in normotensive and hypertensive populations , the tracking of blood pressure from childhood to adult life and the apparent association between birth weight and adult blood pressure. Notably, twin studies have not been able to shed significant light on the question of whether the birth weight-blood pressure association is due to genetic or environmental factors[38]. Influence of childhood hypertension on adult markers of cardiovascular disease Of more practical value than the issue of what generates high blood pressure is the question whether childhood hypertension is a predictor or an actual cause of adult cardiovascular disease. "

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