| 1. |
- Barker, Adam, et al.
(författare)
-
Association of genetic loci with glucose levels in childhood and adolescence a meta-analysis of over 6,000 children
- 2011
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:6, s. 1805-1812
-
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
|
|
| 2. |
- den Hoed, Marcel, 1980-, et al.
(författare)
-
Genetic susceptibility to obesity and related traits in childhood and adolescence influence of loci identified by genome-wide association studies
- 2010
-
Ingår i: Diabetes. - Alexandria, USA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:11, s. 2980-2988
-
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
|
|
| 3. |
- Ong, Ken K., et al.
(författare)
-
Genetic variation in LIN28B is associated with the timing of puberty
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
-
Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
|
|
| 4. |
- Kelliny, Clara, et al.
(författare)
-
Common genetic determinants of glucose homeostasis in healthy children : the European youth heart study
- 2009
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 58:12, s. 2939-2945
-
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
|
|
| 5. |
- Kilpelaeinen, Tuomas O., et al.
(författare)
-
Obesity-susceptibility loci have a limited influence on birth weight : a meta-analysis of up to 28,219 individuals
- 2011
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:4, s. 851-860
-
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.
|
|
| 6. |
- Ekelund, Ulf, et al.
(författare)
-
Association of weight gain in infancy and early childhood with metabolic risk in young adults
- 2007
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 98-103
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. OBJECTIVE: The aim of this study was to examine the independent associations between weight gain during infancy (0-6 months) and early childhood (3-6 yr) with components of the metabolic syndrome in young adults. DESIGN: This was a prospective cohort study (The Stockholm Weight Development Study). SETTING: The study was conducted in a general community. PARTICIPANTS: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain during infancy (standardized beta = 0.16; P < 0.0001) but not during early childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight, gestational age, current height, maternal fat mass, and socioeconomic status at age 17 yr. Further adjustment for current fat mass and weight gain during childhood did not alter the significant association between infancy weight gain with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS: Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6 yr) predicted clustered metabolic risk at age 17 yr. Early interventions to moderate rapid weight gain even at very young ages may help to reduce adult cardiovascular disease risks.
|
|
| 7. |
- Ekelund, Ulf, 1960-, et al.
(författare)
-
Does physical activity equally predict gain in fat mass among obese and nonobese young adults?
- 2007
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 31:1, s. 65-71
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Differences in energy metabolism and physical activity (PA) may contribute to the long-term regulation of body weight (BW).OBJECTIVE: To examine the associations between metabolic determinants, energy expenditure and objectively measured components of PA with change in BW and fat mass (FM). DESIGN: Prospective (4 years.), case-control study in obese (n=13) and normal weight (n=15) young adults.MEASUREMENTS: At baseline, we measured resting metabolic rate, substrate oxidation, movement economy (ml O(2) kg(-1) min(-1)), aerobic fitness (VO(2max)), total and PA energy expenditure by doubly labelled water, and PA by accelerometry. Fat mass was measured by DXA. At follow-up we repeated our measurements of PA and FM.RESULTS: Fat mass increased significantly (P<0.001) in both groups. Physical activity did not change between baseline and 'follow up'. Change in overall PA (counts per minute) was inversely associated with change in BW and (beta=-0.0124, P=0.054) and FM (beta=-0.008, P=0.04). Post hoc analyses suggested that this association was explained by changes in the normal weight group only (beta=-0.01; P=0.008; and beta=-0.0097; P=0.009, for BW and FM, respectively). Metabolic determinants, energy expenditure estimates and subcomponents of PA (i.e. time spent at different intensity levels) were not significantly associated with change in BW or FM.CONCLUSION: Our results suggest an independent association between PA and FM. However, this association may differ depending on obesity status. The gain in FM, without any change in PA, may suggest that dietary intake is the major contributor to the positive energy balance.
|
|
