| 1. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 2. |
- Silventoinen, Karri, et al.
(författare)
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Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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| 3. |
- Silventoinen, Karri, et al.
(författare)
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The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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| 4. |
- Barker, Adam, et al.
(författare)
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Association of genetic loci with glucose levels in childhood and adolescence a meta-analysis of over 6,000 children
- 2011
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:6, s. 1805-1812
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS-A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS-Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS-Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards. Diabetes 60:1805-1812, 2011
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| 5. |
- den Hoed, Marcel, 1980-, et al.
(författare)
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Genetic susceptibility to obesity and related traits in childhood and adolescence influence of loci identified by genome-wide association studies
- 2010
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Ingår i: Diabetes. - Alexandria, USA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:11, s. 2980-2988
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Large-scale genome-wide association (GWA) studies have thus far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children and adolescents.Research design and methods: Seventeen variants representing 16 obesity susceptibility loci were genotyped in 1,252 children (mean +/- SD age 9.7 +/- 0.4 years) and 790 adolescents (15.5 +/- 0.5 years) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by summing the number of effect alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analyzed with previously reported data (N-total = 13,071 children and adolescents). Results: In EYHS, 15 variants showed associations or trends with anthropometric traits that were directionally consistent with earlier reports in adults. The meta-analysis showed directionally consistent associations with BMI for all 13 variants, of which 9 were significant (0.033-0.098 SD/allele; P < 0.05). The near-TMEM18 variant had the strongest effect (0.098 SD/allele P = 8.5 x 10(-11)). Effect sizes for BMI tended to be more pronounced in children and adolescents than reported earlier in adults for variants in or near SEC16B, TMEM18, and KCTD15, (0.028-0.035 SD/allele higher) and less pronounced for rs925946 in BDNF (0.028 SD/allele lower). Each additional effect allele in the GPS-17 was associated with an increase of 0.034 SD in BMI (P = 3.6 x 10(-5)), 0.039 SD, in sum of skinfolds (P = 1.7 x 10(-7)), and 0.022 SD in waist circumference (P = 1.7 X 10(-4)), which is comparable with reported results in adults (0.039 SD/allele for BMI and 0.033 SD/allele for waist circumference).Conclusions: Most obesity susceptibility loci identified by GWA studies in adults are already associated with anthropometric traits in children/adolescents. Whereas the association of some variants may differ with age, the cumulative effect size is similar. Diabetes 59:2980-2988, 2010
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| 6. |
- Kelliny, Clara, et al.
(författare)
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Common genetic determinants of glucose homeostasis in healthy children : the European youth heart study
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 58:12, s. 2939-2945
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-The goal of this study was to investigate whether the effects of common genetic variants associated with fasting glucose in adults are detectable in healthy children. RESEARCH DESIGN AND METHODS-Single nucleotide polymorphisms in MTNR1B (rs10830963), G6PC2 (rs560887), and GCK (rs4607517) were genotyped in 2,025 healthy European children aged 9-11 and 14-16 years. Associations with fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance (IR) and HOMA-B were investigated along with those observed for type 2 diabetes variants available in this study (CDKN2A/B, IGF2BP2, CDKAL1, SLC30A8, HHEX-IDE, and Chr 11p12). RESULTS-Strongest associations were observed for G6PC2 and MTNR1B, with mean fasting glucose levels (95% Cl) being 0.084 (0.06-0.11) mmol/l, P = 7.9 x 10(-11) and 0.069 (0.04-0.09) mmol/l, p = 1.9 x 10(-7) higher per risk allele copy, respectively. A similar but weaker trend was observed for GCK (0.028 [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower P-cell function (HOMA-B P = 9.38 x 10(-5), 0.004, and 0.04, respectively). SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher fasting glucose (0.033 mmol/l [0.01-0.06], P = 0.01). Calculating a genetic predisposition score adding the number of risk alleles of G6PC2, MTNR1B, GCK, and SLC30A8 showed that glucose levels were successively higher in children carrying a greater number of risk alleles (P = 7.1 x 10(-17)), with mean levels of 5.34 versus 4.91 mmol/l comparing children with seven alleles (0.6% of all children) to those with none (0.5%). No associations were found for fasting insulin or HOMA-IR with any of the variants. CONCLUSIONS-The effects of common polymorphisms influencing fasting glucose are apparent in healthy children, whereas the presence of multiple risk alleles amounts to a difference of >1 SD of fasting glucose. Diabetes 58:2939-2945, 2009
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| 7. |
- Kilpelaeinen, Tuomas O., et al.
(författare)
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Obesity-susceptibility loci have a limited influence on birth weight : a meta-analysis of up to 28,219 individuals
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:4, s. 851-860
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Tidskriftsartikel (refereegranskat)abstract
- Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (beta +/- SE: 213 +/- 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (beta +/- SE: 11 +/- 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity. Am J Clin Nutr 2011;93:851-60.
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