Novel Genetic Determinants of Dental Maturation in Children.

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10-8), 14q13.3 (PAX9: P = 1.9 × 10-8), and 16q12.2 (IRX5: P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

Infant dietary patterns and bone mass in childhood: the Generation R Study.

UNLABELLED: Early life nutrition affects peak bone mass attainment. In this prospective cohort study, children with high adherence to a "dairy and whole grains" pattern in infancy had higher bone mineral density at the age of 6 years. Although the observed effects are small, our study provides insight into mechanisms linking early nutrition to bone acquisition in childhood. INTRODUCTION: Nutrition in early life may affect peak bone mass attainment. Previous studies on childhood nutrition and skeletal health mainly focused on individual nutrients, which does not consider the cumulative effects of nutrients. We investigated the associations between dietary patterns in infancy and childhood bone health. METHODS: This study included 2850 children participating in a population-based prospective cohort study. Dietary information was obtained from a food frequency questionnaire at the age of 13 months. Using principal component analysis, three major dietary patterns were extracted, explaining in total 30% of the variation in dietary intake. At the age of 6 years, a total body dual-energy X-ray absorptiometry (DXA) scan was performed, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC), and bone area (BA) were analyzed. RESULTS: Higher adherence score to a "dairy and whole grains" pattern was positively associated with BMD and aBMC, but not with BMC and BA. Accordingly, children in the highest quartile of the "dairy and whole grains" pattern had higher BMD (difference 3.98 mg/cm(2), 95% confidence interval (CI) 0.36 to 7.61) and aBMC (difference 4.96 g, 95% CI 1.27 to 8.64) than children in the lowest quartile. Stratification for vitamin D supplementation showed that the positive associations between the "dairy and whole grains" pattern and bone outcomes were only observed in children who did not receive vitamin D supplementation. A "potatoes, rice, and vegetables" and a "refined grains and confectionery" pattern were not consistently associated with bone outcomes. CONCLUSIONS: An infant dietary pattern characterized by high intakes of dairy and cheese, whole grains, and eggs is positively associated with bone development in childhood. Further research is needed to investigate the consequences for bone health in later life.

Does fetal smoke exposure affect childhood bone mass? The Generation R Study.

UNLABELLED: We assessed the intrauterine influence of maternal smoking on childhood bone mass by comparing parental prenatal and postnatal smoking habits. We observed higher bone mass in children exposed to maternal smoking, explained by higher body weight. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth. INTRODUCTION: Maternal smoking during pregnancy may adversely affect bone health in later life. By comparing the associations of maternal and paternal smoking and of prenatal and postnatal exposure with childhood bone measures, we aimed to explore whether the suggested association could be explained by fetal programming or reflects confounding by familial factors. METHODS: In 5565 mothers, fathers and children participating in a population-based prospective cohort study, parental smoking habits during pregnancy and current household smoking habits were assessed by postal questionnaires. Total body bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA) at the median age of 6.0 years (IQR 0.37). RESULTS: In confounder-adjusted models, maternal smoking during pregnancy was associated with a higher BMC of 11.6 g (95 % confidence interval (CI) 5.6, 17.5), a larger BA of 9.7 cm(2) (95 % CI 3.0, 16.4), a higher BMD of 6.7 g/cm(2) (95 % CI 2.4, 11.0) and a higher BMC of 5.4 g (95 % CI 1.3, 9.6) adjusted for BA of the child. Current weight turned out to mediate these associations. Among mothers who did not smoke, paternal smoking did not show evident associations with childhood bone measures. Also, household smoking practices during childhood were not associated with childhood bone measures. CONCLUSIONS: Our results do not support the hypothesis of fetal smoke exposure affecting childhood bone mass via intrauterine mechanisms. Maternal smoking or related lifestyle factors may affect childhood weight gain rather than skeletal growth.