Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD.

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%).

Associations of breast-feeding patterns and introduction of solid foods with childhood bone mass: The Generation R Study.

Breast-feeding has been associated with later bone health, but results from previous studies are inconsistent. We examined the associations of breast-feeding patterns and timing of introduction of solids with bone mass at the age of 6 years in a prospective cohort study among 4919 children. We collected information about duration and exclusiveness of breast-feeding and timing of introduction of any solids with postnatal questionnaires.

Bone Mass and Strength in School-Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study.

Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school-age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole-body and hip scans were measured using the same densitometer (GE-Lunar iDXA) at a mean age of 6.

BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures.

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry.

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent.

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.

Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

Context: Higher infant growth rates are associated with an increased risk of obesity in later life.

Objective: We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood.

Design, Setting, And Participants: We performed a population-based prospective cohort study among 6464 children.

General and abdominal fat outcomes in school-age children associated with infant breastfeeding patterns.

Background: Breastfeeding may have a protective effect on the development of obesity in later life. Not much is known about the effects of infant feeding on more-specific fat measures.

Objective: We examined associations of breastfeeding duration and exclusiveness and age at the introduction of solid foods with general and abdominal fat outcomes in children.

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

Background: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants.

Objective: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies.

Design: The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies.

Maternal first-trimester diet and childhood bone mass: the Generation R Study.

Background: Maternal diet during pregnancy has been suggested to influence bone health in later life.

Objective: We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass.

Design: In a prospective cohort study in 2819 mothers and their children, we measured first-trimester daily energy, protein, fat, carbohydrate, calcium, phosphorus, and magnesium intakes by using a food-frequency questionnaire and homocysteine, folate, and vitamin B-12 concentrations in venous blood.

Maternal first-trimester dietary intake and childhood blood pressure: the Generation R Study.

Suboptimal maternal dietary intake during pregnancy might lead to fetal cardiovascular adaptations and higher blood pressure in the offspring. The aim of the present study was to investigate the associations of maternal first-trimester dietary intake with blood pressure in children at the age of 6 years. We assessed first-trimester maternal daily dietary intake by a FFQ and measured folate, homocysteine and vitamin B₁₂ concentrations in the blood, in a population-based prospective cohort study among 2863 mothers and children.

Parental, fetal, and infant risk factors for preschool overweight: the Generation R Study.

Background: Overweight has its origins largely in early life. We aimed to identify the most important parental, fetal, and infant risk factors of preschool overweight.

Methods: In a prospective cohort study, among 3,610 Caucasian preschool children, we assessed the associations of 34 putative parental, fetal, and infant factors with overweight risk.

Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus.

To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.

Maternal milk consumption, fetal growth, and the risks of neonatal complications: the Generation R Study.

Background: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth.

Objective: The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications.

Maternal fish consumption, fetal growth and the risks of neonatal complications: the Generation R Study.

Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age.