Dataset Information

Genetic variations in the serotoninergic system contribute to body-mass index in Chinese adolescents.

ABSTRACT:

Objective

Obesity has become a worldwide health problem in the past decades. Human and animal studies have implicated serotonin in appetite regulation, and behavior genetic studies have shown that body mass index (BMI) has a strong genetic component. However, the roles of genes related to the serotoninergic (5-hydroxytryptamine,5-HT) system in obesity/BMI are not well understood, especially in Chinese subjects.

Subjects and design

With a sample of 478 healthy Chinese volunteers, this study investigated the relation between BMI and genetic variations of the serotoninergic system as characterized by 136 representative polymorphisms. We used a system-level approach to identify SNPs associated with BMI, then estimated their overall contribution to BMI by multiple regression and verified it by permutation.

Results

We identified 12 SNPs that made statistically significant contributions to BMI. After controlling for gender and age, four of these SNPs accounted for 7.7% additional variance of BMI. Permutation analysis showed that the probability of obtaining these findings by chance was low (p = 0.015, permuted for 1000 times).

Conclusion

These results showed that genetic variations in the serotoninergic system made a moderate contribution to individual differences in BMI among a healthy Chinese sample, suggesting that a similar approach can be used to study obesity.

SUBMITTER: Chen C

PROVIDER: S-EPMC3598805 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variations in the serotoninergic system contribute to body-mass index in Chinese adolescents.

Chen Chunhui C Chen Wen W Chen Chuansheng C Moyzis Robert R He Qinghua Q Lei Xuemei X Li Jin J Wang Yunxin Y Liu Bin B Xiu Daiming D Zhu Bi B Dong Qi Q

PloS one 20130315 3

<h4>Objective</h4>Obesity has become a worldwide health problem in the past decades. Human and animal studies have implicated serotonin in appetite regulation, and behavior genetic studies have shown that body mass index (BMI) has a strong genetic component. However, the roles of genes related to the serotoninergic (5-hydroxytryptamine,5-HT) system in obesity/BMI are not well understood, especially in Chinese subjects.<h4>Subjects and design</h4>With a sample of 478 healthy Chinese volunteers, t ...[more]

PMID: 23554917

Similar Datasets

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.

Project description:ImportanceThere is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower.ObjectivesTo compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status.Design, setting, and participantsThis cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019.ExposuresMeasured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations.Main outcomes and measuresIncident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score.ResultsAmong 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status.Conclusions and relevanceIn this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.

Project description: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.

Dataset Information

Genetic variations in the serotoninergic system contribute to body-mass index in Chinese adolescents.

Objective

Subjects and design

Results

Conclusion

Publications

Genetic variations in the serotoninergic system contribute to body-mass index in Chinese adolescents.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets