Showing papers by "Andy R Ness published in 2009"

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Genetic variation in LIN28B is associated with the timing of puberty

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 a ...

Infancy weight gain predicts childhood body fat and age at menarche in girls.

Abstract: Context: Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity. However, the contribution of rapid weight gain during specific infancy periods is not clear. Objective: We aimed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls. Design, Setting, and Participants: A total of 2715 girls from a prospective UK birth cohort study participated in the study. Main Outcome Measures: Routinely measured weights and lengths at ages 2, 9, and 19 months were extracted from the local child health computer database. Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr, and age at menarche was assessed by questionnaire (categorized into three groups: 13.0 yr). Results: Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche...

Prospective associations between objective measures of physical activity and fat mass in 12-14 year old children: the Avon Longitudinal Study of Parents and Children (ALSPAC)

Abstract: Objective To investigate associations between physical activity at age 12 and subsequent adiposity at age 14. Design Prospective birth cohort study with data collected between 2003 and 2007. Setting Original recruitment in 1991-2 of 14 541 pregnant women living in the former County of Avon (United Kingdom). Participants At age 12, 11 952 children were invited to attend the research clinic. Of these, 7159 attended, and 4150 (1964 boys, 2186 girls) provided sufficient data on exposure, outcome, and confounding variables. Main outcome measure Fat mass at age 14, measured by dual emission x ray absorptiometry, associated with physical activity at age 12, measured by accelerometry. Results Prospective associations of fat mass at age 14 (outcome) with physical activity at age 12 (exposure) were strong for both total activity (accelerometer counts/min) and for daily amount of moderate-vigorous physical activity (min/day). An extra 15 minutes of moderate-vigorous physical activity per day at age 12 was associated with lower fat mass at age 14 in boys (by 11.9% (95% confidence interval 9.5% to 14.3%)) and girls (by 9.8% (6.7% to 12.8%)). The proportion of physical activity due to moderate-vigorous physical activity was between 20% and 30% in boys and girls at the two ages. Conclusions Higher levels of physical activity, in particular activity of moderate to higher intensities, are prospectively associated with lower levels of fat mass in early adolescence. Interventions to raise levels of physical activity in children are likely to be important in the fight against obesity.

Sedentary Behavior and Obesity in a Large Cohort of Children

Abstract: The purpose of this study was to examine the association between sedentary behavior and obesity among 12-year-old children, while adjusting for moderate-to-vigorous physical activity (MVPA) and other potential confounding variables. Cross-sectional analyses were carried out with data from 5,434 children who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). Fat mass was derived using dual-energy X-ray emission absorptiometry, and height and weight measurements were used to calculate BMI (kg/m(2)). The children wore an accelerometer for 7 days. The cut points for sedentary behavior and MVPA were or=3,600 counts per minute (cpm), respectively. Logistic regression analyses were performed to estimate odds ratios (ORs), adjusting for potential confounders of physical activity that included gender, social factors, early life factors, and maturation. The minimally adjusted association between sedentary behavior and obesity was positive, OR = 1.18 (1.08, 1.28). After adjusting for the series of potential confounders of physical activity the positive association remained, OR = 1.32 (1.14, 1.53). The crude association between 15 min of MVPA per day and obesity was negative, OR = 0.54 (0.48, 0.62). When 15 min of MVPA per day was additionally controlled for in the models, the positive associations between sedentary behavior and obesity were negated. Sedentary behavior was positively associated with obesity in the 12-year-old children, but this association was not independent of MVPA; low levels of MVPA among the sedentary children increased the odds of obesity. These findings support the importance of specifically engaging in MVPA during childhood to reduce the prevalence of obesity.

Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants

Abstract: Background: Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants.Methods and Findings: We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (beta = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35+/-0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16+/-0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity.Conclusions: This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.

The management of otitis media with early routine insertion of grommets in children with cleft palate -- a systematic review.

Abstract: Objective: To determine whether early routine grommet insertion in children with cleft palate has a beneficial effect on hearing and speech and language development compared with conservative management. Design: Systematic review of randomized controlled trials, controlled clinical trials, case series, and prospective and historical cohort studies. Main Outcome Measures: The main outcome measure was the effect of early routine grommet placement on the degree of conductive hearing loss. Secondary outcome measures included differences in hearing level, possible side effects, speech and language development, and quality of life. Results: We identified 368 citations for review. From a review of the titles, 34 potentially relevant papers were selected. Of these, 18 studies met our inclusion criteria, including eight case series, six historical cohort studies, three prospective cohort studies, and one randomized trial. Most studies were either small or of poor quality or both. The results of the studie...

Association of duration of television viewing in early childhood with the subsequent development of asthma

Abstract: Objectives: To investigate whether duration of television (TV) viewing in young children is associated with subsequent development of asthma. Design: Prospective longitudinal cohort study. Setting: Avon Longitudinal Study of Parents and Children (ALSPAC), United Kingdom. Participants: Children taking part in Avon Longitudinal Study of Parents and Children (ALSPAC) with no wheeze up to 3 ½ years with follow up data at 11 ½ years. Main outcome measures: Asthma defined as: Doctor diagnosed asthma by 7 ½ years with symptoms and/or treatment in last 12 months at 11 ½ years. Parental report of hours of children’s television viewing per day was ascertained at 39 months. Results: In children asymptomatic for wheeze to 3½ years with follow up data at 11½ years, asthma prevalence was 6% (185/3065). Increased TV viewing at 3 ½ years was associated with increased prevalence of asthma at 11 ½ years (p for linear trend=0.0003). Children who watched television for more than 2 hours per day were almost twice as likely to develop asthma by 11 ½ years than those watching <2 hours TV per day (Adjusted Odds Ratio (AOR) (95% Confidence Interval) 1.8 (1.2 to 2.6)). Conclusion: Longer duration of TV viewing in children asymptomatic for wheeze at 3½ years was associated with the development of asthma in later childhood.

Life course sun exposure and risk of prostate cancer: population-based nested case-control study and meta-analysis.

Abstract: There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet-radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK-wide nested case-control study, based on 1,020 prostate specific antigen-detected cases and 5,044 matched population controls and a systematic review with meta-analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta-analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random-effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random-effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta-analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials.

Challenges and novel approaches in the epidemiological study of early life influences on later disease.

Abstract: The influence of factors acting during early life on health outcomes of offspring is of considerable research and public health interest. There are, however, methodological challenges in establishing robust causal links, since exposures often act many decades before outcomes of interest, and may also be strongly related to other factors, generating considerable degrees of potential confounding. With respect to pre-natal factors, the degree of confounding can sometimes be estimated by comparing the association between exposures experienced by the mother during pregnancy and outcomes among the offspring with the association of the same exposures experienced by the father during the pregnancy period and offspring outcomes. If the effects are due to an intra-uterine exposure, then maternal exposure during pregnancy should have a clearly greater influence than paternal exposure. If confounding by socio-economic, behavioural or genetic factors generates the association then maternal and paternal pregnancy exposures will be related in the same way with the outcome. For early life exposures it is also possible to compare outcomes in siblings who are concordant or discordant for the exposure, which will reduce the influence of family-level confounding factors. A different approach is that of Mendelian randomization, which utilises genetic variants of known effect that can proxy for modifiable exposures and are also not in general related to potential confounding factors, or influenced by disease. In other settings the use of non-genetic instrumental variables is possible. A series of examples of the application of these approaches are presented and their potentials and limitations discussed. Other epidemiological strategies are briefly reviewed. It is concluded that the naive acceptance of findings utilising conventional epidemiological methods in this setting is misplaced.

Comparison of waist circumference percentiles versus body mass index percentiles for diagnosis of obesity in a large cohort of children

Abstract: Context. Waist circumference may offer improved diagnosis of obesity in youth compared with body mass index (BMI), but empirical evidence is limited. Objective. To compare the ability of BMI percentile using UK reference data and waist circumference percentile using UK reference data to diagnose high fat mass in English children. Design and Methods. In 7 722 9–10-year-olds (3 809 boys, 3 913 girls) sensitivity and specificity were calculated and receiver operator characteristic (ROC) analyses undertaken to determine the diagnostic accuracy of BMI and waist circumference z-scores to define high fat mass measured by dual energy x-ray absorptiometry (DXA). High fat mass was defined as being in the top decile of fatness for each sex (359 boys and 367 girls). Results. The area under the ROC curve was slightly higher for BMI percentile (0.92 in boys, 95% CI: 0.91 –0.93; 0.94 in girls, 95% CI: 0.93–0.95) than waist circumference percentile (0.89 in boys, 95% CI: 0.86–0.91; 0.81 in girls, 95% CI: 0.73–0.9...

Body composition at age 9 years, maternal folate intake during pregnancy and methyltetrahydrofolate reductase (MTHFR) C677T genotype.

Abstract: Nutrition during pregnancy and in early life may influence developmental plasticity and alter susceptibility to obesity and adult disease. One mechanism by which this could occur is through epigenetic changes, such as changes in methylation levels, which modify gene expression patterns. Folate intake during pregnancy, as well as maternal methyltetrahydrofolate reductase (MTHFR) C677T genotype, influences the availability of methyl donors for methylation during gestation and therefore may be associated with offspring body composition in childhood. We looked at associations between maternal folic acid supplementation at 18 and 32 weeks of pregnancy, folate intake in the diet (from self-reported FFQ) at 32 weeks of pregnancy and offspring body composition at age 9 years among 5783 children from a population-based birth cohort study in the UK. We also looked at maternal and offspring's MTHFR C677T genotype in relation to offspring body composition. We found no evidence to support the hypothesis that intra-uterine exposure to folate influences childhood body composition.

Validation of dual-energy x-ray absorptiometry and foot-foot impedance against deuterium dilution measures of fatness in children

Abstract: Objective. To determine the validity of estimation of body fatness by dual-energy x-ray absorptiometry (DXA) and foot-foot bio-electrical impedance (BIA). Methods. In 176, 11–12-year-olds (84 boys;...

Myopia and later physical activity in adolescence: a prospective study

Abstract: Objectives: To investigate associations between objectively measured physical activity (PA) and myopia in children. Methods: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were asked to wear a uniaxial accelerometer for 7 days. Measures of counts per minute (cpm), minutes spent in moderate to vigorous activity (MVPA) and minutes of sedentary behaviour (msed) were derived from the accelerometer worn at age 12. Children were also examined, at age 10, using an autorefractor to estimate myopia. Social and parental factors were collected from pregnancy and physical measures of the child were recorded at age 12. Results: 4880 children had valid PA and autorefraction data. In minimally adjusted models (age and gender) myopic children were less active than the other children: β = −49.9 cpm (95% CI −73.5 to −26.4, p = Conclusion: Myopic children may be more at risk of having lower levels of PA than their non-myopic peers, although the difference was modest.