Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetesâsusceptibility genes identified a common variant in the
FTO
(fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational
prospective observational study investigating influences on health and development across
the life course. It considers multiple genetic, epigenetic, biological, psychological,
social and other environmental exposures in relation to a similarly diverse range of
health, social and developmental outcomes. Recruitment sought to enrol pregnant women in
the Bristol area of the UK during 1990–92; this was extended to include additional
children eligible using the original enrolment definition up to the age of 18 years. The
children from 14 541 pregnancies were recruited in 1990–92, increasing to
15 247 pregnancies by the age of 18 years. This cohort profile describes the index
children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks–18
years of age) and 9 clinical assessment visits (7–17 years of age). The resource
comprises a wide range of phenotypic and environmental measures in addition to biological
samples, genetic (DNA on 11 343 children, genome-wide data on 8365 children,
complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000
children) information and linkage to health and administrative records. Data access is
described in this article and is currently set up as a supported access resource. To date,
over 700 peer-reviewed articles have been published using ALSPAC data.
Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was
established to understand how genetic and environmental characteristics influence health
and development in parents and children. All pregnant women resident in a defined area in
the South West of England, with an expected date of delivery between 1st April 1991 and
31st December 1992, were eligible and 13 761 women (contributing 13 867
pregnancies) were recruited. These women have been followed over the last 19–22
years and have completed up to 20 questionnaires, have had detailed data abstracted from
their medical records and have information on any cancer diagnoses and deaths through
record linkage. A follow-up assessment was completed 17–18 years postnatal at which
anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness
were assessed, and a fasting blood sample taken. The second follow-up clinic, which
additionally measures cognitive function, physical capability, physical activity (with
accelerometer) and wrist bone architecture, is underway and two further assessments with
similar measurements will take place over the next 5 years. There is a detailed biobank
that includes DNA, with genome-wide data available on >10 000, stored serum and
plasma taken repeatedly since pregnancy and other samples; a wide range of data on
completed biospecimen assays are available. Details of how to access these data are
provided in this cohort profile.
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 × 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.
Although null findings may be underreported the results are consistent with a strong protective effect of fruit and vegetables for stroke and a weaker protective effect on coronary heart disease. Greater use of food-based hypotheses and analyses, would complement existing nutrient-based analyses and help guide the search for underlying causes.
Ruth Loos and colleagues report findings from a meta-analysis of multiple studies examining the extent to which physical activity attenuates effects of a specific gene variant, FTO, on obesity in adults and children. They report a fairly substantial attenuation by physical activity on the effects of this genetic variant on the risk of obesity in adults.
Objective: To measure the levels and patterns of physical activity, using accelerometers, of 11-year-old children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Design: Cross-sectional analysis. Setting: ALSPAC is a birth cohort study located in the former county of Avon, in the southwest of England. This study used data collected when the children were 11 years old. Participants: 5595 children (2662 boys, 2933 girls). The children are the offspring of women recruited to a birth cohort study during 1991-2. The median age (95% CI) of the children is now 11.8 (11.6 to 11.9) years. Methods: Physical activity was measured over a maximum of 7 consecutive days using the MTI Actigraph accelerometer. Main outcome measures: Level and pattern of physical activity. Results: The median physical activity level was 580 counts/min. Boys were more active than girls (median (IQR) 644 (528-772) counts/min vs 529 (444-638) counts/min, respectively). Only 2.5% (95% CI 2.1% to 2.9%) of children (boys 5.1% (95% CI 4.3% to 6.0%), girls 0.4% (95% CI 0.2% to 0.7%) met current internationally recognised recommendations for physical activity. Children were most active in summer and least active in winter (difference = 108 counts/min). Both the mother and partner's education level were inversely associated with activity level (p for trend ,0.001 (both mother and partner)). The association was lost for mother's education (p for trend = 0.07) and attenuated for partner's education (p for trend = 0.02), after adjustment for age, sex, season, maternal age and social class. Conclusions: A large majority of children are insufficiently active, according to current recommended levels for health.
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