Most genome-wide association studies are confined to middle-aged populations. It is unclear whether associations between single nucleotide polymorphisms (SNPs) and obesity persist in old age. We aimed to relate 10 body mass index (BMI)-associated SNPs to weight, BMI, % fat, visceral and subcutaneous adipose tissue in Health ABC and AGES-Reykjavik comprising 4,846 individuals of European Ancestry, and 1,139 African Americans over age 65. SNPs were scaled using effect estimates from candidate SNPs. In Health ABC, a SNP near GNPDA2 was modestly associated with weight and SAT area (p = .008, p = .001). Risk score (sum of scaled SNPs) was associated with weight, BMI, and SAT area (p
Cites: Nat Genet. 2010 Nov;42(11):949-6020935629
Cites: Lancet. 2010 Oct 23;376(9750):1393-40020971364
Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.
Maternal overweight and obesity during pregnancy, and childhood growth patterns are risk factors influencing long-term health outcomes among the offspring. Furthermore, poor health condition has been associated with shorter leukocyte telomere length in adult subjects. We aimed to assess whether maternal adiposity during pregnancy and growth trajectory during infancy predict leukocyte telomere length (LTL) in later life.
We studied a cohort of 1082 subjects belonging to the Helsinki Birth Cohort Study, born between 1934 and 1944. They underwent two clinical visits 10 years apart (2001-2004 and 2011-2013), during which LTL and anthropometrics were assessed. Birth records included birth weight, length, maternal body mass index (BMI) at the end of pregnancy. Serial measurements of height and weight from birth to 11 years were available.
Higher maternal BMI was associated with shorter LTL in elderly women (r=-0.102, P=0.024) but not in men. Also, in women but not in men shorter LTL and greater telomere shortening over a 10-year interval were predicted by higher weight at 12 months of age (P=0.008 and P=0.029, respectively), and higher weight gain during the first 12 months of life (P=0.008 and P=0.006, respectively), particularly between 6 and 9 months of age (P=0.002 for both LTL and LTL shortening rate). A correlation between younger age at adiposity rebound and shorter LTL at 60 years (P=0.022) was also found.
High maternal adiposity during pregnancy is associated with shorter LTL in elderly female offspring, but not in men. Moreover, higher weight and weight gain during the first year of life and younger age at adiposity rebound predict shorter LTL in older age in women, suggesting that rapid growth during the perinatal period accelerates cellular aging in late adulthood.
Cites: Am J Clin Nutr. 2008 Jun;87(6):1769-7518541567
Cites: Int J Obes (Lond). 2006 Aug;30(8):1281-716505835
The impact of previously identified genetic variants directly or indirectly associated with obesity, were investigated at birth, adolescence and adulthood to provide knowledge concerning timing and mechanisms of obesity susceptibility with focus on sex differences.
Twenty four previously identified obesity- and eating disorder susceptibility loci were tested for association with adiposity traits at birth (ponderal index (PI)), adolescence and young adulthood (body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR)) in 1782 individuals from the HUNT study. Single-nucleotide polymorphism (SNPs) were evaluated individually and by haplotype sliding-window approach for windows?50?kb (near-MC4R, FTO and near-BDNF). The analyses were performed on the total and sex stratified samples.
The most substantial effect on BMI was observed for the near-MC4R variants at adolescence and adulthood (adjusted P-values in adolescence: 0.002 and 0.003 for rs17782313 and rs571312, respectively). The same variants showed inverse association with PI in males (adjusted P-values: 0.019-0.036). Furthermore, significant effects were observed at adolescence with BMI for the near-KCTD15 variant (rs11084753) (adjusted P=0.038) in the combined sample. The near-INSIG2 (rs7566605) was significantly associated to WHR in males and near-BDNF (rs925946) in the combined sample (adjusted P=0.027 and P=0.033, respectively). The OPRD1 locus was associated to BMI and WC in males both at adolescence and adulthood with highest effect in adults (adjusted P=0.058). Interaction with sex was identified for near-MC4R, OPRD1, COMT, near-BDNF and DRD2.
Most obesity susceptibility variants show stronger effect at adolescence than at birth and adulthood with a clear sex-specific effect at some loci. The near-MC4R locus exhibit inverse effect on weight at birth in boys compared with findings at adolescence and adulthood. Some variants less known for obesity-susceptibility such as OPRD1 were found to be associated to weight with strongest effects in males.