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Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study.

ABSTRACT: BACKGROUND:Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans-a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population. OBJECTIVE:To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR, MC4R, NPY2R and POMC genes. DESIGN:A genetic association study. PARTICIPANTS:990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans). MEASURES:The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population for FTO, LEP and NPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life. RESULTS:Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI. CONCLUSIONS:The study highlighted SNPs in FTO and MC4R as potential genetic markers of obesity risk in South Africans. The association with two SNPs in the 3' untranslated region of the LEP gene is novel.

SUBMITTER: Lombard Z

PROVIDER: S-EPMC3358621 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study.

Lombard Zané Z Crowther Nigel J NJ van der Merwe Lize L Pitamber Punita P Norris Shane A SA Ramsay Michèle M

BMJ open 20120521 3

<h4>Background</h4>Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans-a single genome-wide association study and a few replication studies have been published in West Africa, but none have been perf ...[more]

PMID: 22614171

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Project description:Background/objectivesBody mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children.MethodsWe used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments.ResultsWe restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI.ConclusionsBMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

Project description:What is already known about this subjectRates of childhood obesity have increased since the mid-1970s. Research into behavioural determinants has focused on physical inactivity and unhealthy diets. Cross-sectional studies indicate an association between psychological stress experienced by parents and obesity in pre-adolescents.What this study addsWe provide evidence of a prospective association between parental psychological stress and increased weight gain in pre-adolescents. Family-level support for those experiencing chronic stress might help promote healthy diet and exercise behaviours in children.ObjectiveWe examined the impact of parental psychological stress on body mass index (BMI) in pre-adolescent children over 4 years of follow-up.MethodsWe included 4078 children aged 5-10 years (90% were between 5.5 and 7.5 years) at study entry (2002-2003) in the Children's Health Study, a prospective cohort study in southern California. A multi-level linear model simultaneously examined the effect of parental stress at study entry on the attained BMI at age 10 and the slope of change across annual measures of BMI during follow-up, controlled for the child's age and sex. BMI was calculated based on objective measurements of height and weight by trained technicians following a standardized procedure.ResultsA two standard deviation increase in parental stress at study entry was associated with an increase in predicted BMI attained by age 10 of 0.287 kg m(-2) (95% confidence interval 0.016-0.558; a 2% increase at this age for a participant of average attained BMI). The same increase in parental stress was also associated with an increased trajectory of weight gain over follow-up, with the slope of change in BMI increased by 0.054 kg m(-2) (95% confidence interval 0.007-0.100; a 7% increase in the slope of change for a participant of average BMI trajectory).ConclusionsWe prospectively demonstrated a small effect of parental stress on BMI at age 10 and weight gain earlier in life than reported previously. Interventions to address the burden of childhood obesity should address the role of parental stress in children.

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Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study.

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Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study.

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