Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Innsbruck Medical University, Austria
PLoS ONE (Impact Factor: 3.23). 12/2010; 5(12):e14190. DOI: 10.1371/journal.pone.0014190
Source: PubMed


Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.
Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.
24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.

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    • "Given this, the infant BMI peak may be a useful trait for genetic analysis; known genetic variants associated with BMI and obesity in adults tend to associate fairly weakly with birth weight and ponderal index (Andersson et al., 2010) and with later infancy BMI (Choh et al., 2011). In contrast, a recent study using curve fitting to derive Age Peak and BMI Peak found significantly lower BMI Peak in carriers of a high risk genotype for the obesity gene FTO (Sovio et al., 2011). "
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    ABSTRACT: To characterize an early trait in the BMI-for-age curve, the infant BMI peak. BMI-for-age curves were produced for 747 non-Hispanic, white Fels Longitudinal Study participants, from which individual age (AgePeak ) and BMI (BMIPeak ) at maximum infant BMI were estimated. Multivariable general linear regression was used to examine the effects of sex and birth year cohort (1929-1950, 1951-1970, and 1971-2010) on AgePeak and BMIPeak , with associations between BMIPeak and concurrent sum of four skinfold thicknesses assessed in a subsample (N = 155). Heritability (h(2) ) of AgePeak and BMIPeak was estimated using maximum-likelihood variance components analysis. AgePeak occurred at 9 months of age in both sexes, but BMIPeak was 0.4 kg/m(2) higher for boys than for girls (P-value < 0.001). Infants born between 1971 and 2010 experienced a 1.5 month earlier AgePeak and a 0.35 kg/m(2) lower BMIPeak than infants born between 1929 and 1950 (P-values < 0.001). Skinfold thickness explained 37% of the variance in BMIPeak in boys and 20% of the variance in girls (p-values < 0.001). AgePeak and BMIPeak were significantly heritable (h(2) = 0.54 and 0.75, respectively). Both AgePeak and BMIPeak decreased over successive birth year cohorts in the Fels Longitudinal Study. Despite a positive association of BMIPeak with concurrent adiposity, AgePeak appears to occur later than does the well-documented peak in infant fat mass and BMIPeak does not capture known sex differences in infant adiposity. Strong heritability of these infant BMI traits suggests investigation of genetic control, and validation of their relationship to body composition is greatly needed. Am. J. Hum. Biol. 25:378-388, 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 05/2013; 25(3):378-88. DOI:10.1002/ajhb.22385 · 1.70 Impact Factor
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    • "Current concepts of blood glucose dynamics have been summarised in such models [14,43-45]. For instance, blood glucose levels and, hence, the shapes of glucose curves are affected by a number of key organs and physiologic processes that regulate the entry and removal of glucose from the blood [12,46]. A major disadvantage of parametric models is that estimating each person’s individual parameters requires many measurements, often based on intravenous test procedures [47]. "
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    ABSTRACT: Background Plasma glucose levels are important measures in medical care and research, and are often obtained from oral glucose tolerance tests (OGTT) with repeated measurements over 2–3 hours. It is common practice to use simple summary measures of OGTT curves. However, different OGTT curves can yield similar summary measures, and information of physiological or clinical interest may be lost. Our mean aim was to extract information inherent in the shape of OGTT glucose curves, compare it with the information from simple summary measures, and explore the clinical usefulness of such information. Methods OGTTs with five glucose measurements over two hours were recorded for 974 healthy pregnant women in their first trimester. For each woman, the five measurements were transformed into smooth OGTT glucose curves by functional data analysis (FDA), a collection of statistical methods developed specifically to analyse curve data. The essential modes of temporal variation between OGTT glucose curves were extracted by functional principal component analysis. The resultant functional principal component (FPC) scores were compared with commonly used simple summary measures: fasting and two-hour (2-h) values, area under the curve (AUC) and simple shape index (2-h minus 90-min values, or 90-min minus 60-min values). Clinical usefulness of FDA was explored by regression analyses of glucose tolerance later in pregnancy. Results Over 99% of the variation between individually fitted curves was expressed in the first three FPCs, interpreted physiologically as “general level” (FPC1), “time to peak” (FPC2) and “oscillations” (FPC3). FPC1 scores correlated strongly with AUC (r=0.999), but less with the other simple summary measures (−0.42≤r≤0.79). FPC2 scores gave shape information not captured by simple summary measures (−0.12≤r≤0.40). FPC2 scores, but not FPC1 nor the simple summary measures, discriminated between women who did and did not develop gestational diabetes later in pregnancy. Conclusions FDA of OGTT glucose curves in early pregnancy extracted shape information that was not identified by commonly used simple summary measures. This information discriminated between women with and without gestational diabetes later in pregnancy.
    BMC Medical Research Methodology 01/2013; 13(1):6. DOI:10.1186/1471-2288-13-6 · 2.27 Impact Factor
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    • "One found that the effect of risk alleles of SNPs in the FTO gene was more evident among individuals with low birth weight than among those with high birth weight (30). The other study did not find a significant interaction between birth weight (low, medium, or high) and obesity genotype score (based on 24 SNPs) in prediction of adult BMI in Danish subjects (P for interaction = 0.07) (31). The birth weight–gene interaction in relation to type 2 diabetes was tested in one study based on nine diabetes risk alleles, which showed that the individuals with the lowest birth weight and the most high-risk genotypes had the greatest risk of type 2 diabetes (32). "
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    ABSTRACT: OBJECTIVE Both stressful intrauterine milieus and genetic susceptibility have been linked to later-life diabetes risk. The current study aims to examine the interaction between low birth weight, a surrogate measure of stressful intrauterine milieus, and genetic susceptibility in relation to risk of type 2 diabetes in adulthood.RESEARCH DESIGN AND METHODS The analysis included two independent, nested case-control studies of 2,591 type 2 diabetic case subjects and 3,052 healthy control subjects. We developed two genotype scores: an obesity genotype score based on 32 BMI-predisposing variants and a diabetes genotype score based on 35 diabetes-predisposing variants.RESULTSObesity genotype scores showed a stronger association with type 2 diabetes risk in individuals with low birth weight. In low-birth weight individuals, the multivariable-adjusted odds ratio (OR) was 2.55 (95% CI 1.34-4.84) by comparing extreme quartiles of the obesity genotype score, while the OR was 1.27 (1.04-1.55) among individuals with birth weight >2.5 kg (P for interaction = 0.017). We did not observe significant interaction between diabetes genotype scores and birth weight with regard to risk of type 2 diabetes. In a comparison of extreme quartiles of the diabetes gene score, the multivariable-adjusted OR was 3.80 (1.76-8.24) among individuals with low birth weight and 2.27 (1.82-2.83) among those with high birth weight (P for interaction = 0.16).CONCLUSIONS Our data suggest that low birth weight and genetic susceptibility to obesity may synergistically affect adulthood risk of type 2 diabetes.
    Diabetes care 08/2012; 35(12). DOI:10.2337/dc12-0168 · 8.42 Impact Factor
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