Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty

Abstract

OBJECTIVE: Genome-wide association studies (GWAS) have identified some common variants associated with obesity risk in European descents. However, their influences on obesity-related indices for the Chinese children at puberty are not widely clear yet. To address this question, we conducted a study that aims to examine effects of eight previously reported GWAS singlenucleotide polymorphisms (SNPs) on four obesity-related indices in a sample of Chinese children aged 10 --12 years. METHODS: Anthropometric indices were measured in 1688 children (10.8 ± 0.4 years, boys ¼ 877, girls ¼ 811) from Shanghai Children's Sleep Project. Eight SNPs within the NEGR1, TMEM18, GNPDA2, MTCH2, SH2B1, FTO, MC4R and KCTD15 genes were genotyped using matrix-assisted laser desorption/ionization --time of flight mass spectrometry. Linear regression and genetic additive model were used to test for the association betweens SNPs and obesity-related indices (weight, body mass index (BMI), waist-to-height ratio and body fat). RESULTS: Only two SNPs, rs6548238 (TMEM18) and rs9939609 (FTO), were associated with all obesity-related indices with Po0.05. After adjusting for multiple tests, rs9939609 is the only one significantly associated with the indices. SNPs, rs6548238 and rs9939609 explained 0.28% (P ¼ 0.03) and 0.54% (P ¼ 0.002) variance of BMI, respectively, that are almost two-fold of the previously GWAS-reported effects. In addition, rs6548238 was associated with four indices in boys, but not in girls. In contrast, rs9939609 showed a strong association only in girls. Six other SNPs, rs2815752 (NEGR1), rs10938397 (GNPDA2), rs10838738 (MTCH2), rs7498665 (SH2B1), rs17782313 (MC4R) and rs11084753 (KCTD15), were not associated with obesity (P40.05). CONCLUSIONS: Variants of TMEM18 and FTO are associated with obesity indices during puberty in Chinese children, but candidate SNPs of NEGR1, GNPDA2, MTCH2, SH2B1, MC4R and KCTD15 have no significant effects on obesity indices. The findings also suggest that obesity susceptibility genes may exert more obvious effects during children's puberty. In addition, gender differences may exist in various obesity-related genes.

Associations between a common variant near the MC4R gene and serum triglyceride levels in an obese pediatric cohort

“…One-third of the cohort (n = 173, 33.4 %) was classified as prepubertal, and two-thirds (n = 345, 66.6 %) as pubertal. The median BE scale was 16 [11][12][13][14][15][16][17][18][19][20][21][22], whereas 45.5 % of the cohort was classified with BE. The median insulin level was 20.9 lU/mL (14.7-31.8), and median HOMA-IR was 4.1 (2.8-6.5).…”

“…The Portuguese version of the BE scale [13], the result of a procedure of translation and adaptation, as suggested by Herdman's proposal for cross-cultural adaptation of instruments, showed a sensitivity of 97.8 %, a specificity of 47.7 %, a positive predictive value of 66.7 % and a negative predictive value of 95.3 %. In this study, the participants were categorized into groups of absent BE (BE score B17) and present BE (BE score [17). The assessment of dietary intake of the participants was made using the 24-h dietary recall (24hR) dietary survey, with the objective of evaluating the mean absolute energy intake (kcal), percentage of macronutrients (carbohydrates, protein, total fat), and types of dietary fat (saturated, monounsaturated, and polyunsaturated fats).…”

“…In contrast, our study and others did not confirm these results, since the relationship between this variant did not find an Parametric data presented as mean and standard deviation, compared by Student's t test. Nonparametric data presented as median and 25th and 75th percentiles, compared by Mann-Whitney U test Z-BMI BMI Z score, SBP systolic blood pressure, DBP Diastolic blood pressure [15][16][17], larger waist [15,18], impaired fasting glucose [12], increased insulin levels [15], and hypertension [19]. Qi et al [8] found a higher total energy intake in women homozygous for the C allele than in carriers of the ancestral allele (TT), as well as higher intakes of protein, total fat, and saturated fat.…”

Genetic variations in SEC16B, MC4R, MAP2K5 and KCTD15 were associated with childhood obesity and interacted with dietary behaviors in Chinese school-age population

“…The majority of previous studies are focused on populations of European Ancestry and adults. Subsequent studies have attempted to identify the associations in Chinese population, however, the results of GNPDA2, KCTD15, NEGR1, MC4R, SEC16B and ETV5 are inconsistent (Cheung et al, 2010;Wang et al, 2012;Hong et al, 2013;Xi et al, 2013). In addition, ten other obesity-related genes (LYPLAL1, MSRA, TFAP2B, MAP2K5, RPL27A, PAX5, CDKAL1, AMD1, HOXB5 and OLFM4) have not been examined in Chinese children.…”

Association of single nucleotide polymorphism Rs2236518 in PRDM16 gene with BMI in Chinese males

“…Xi et al [22] confirmed the synthetic effect of SNPs on the indices of adiposity and risk of obesity in Chinese girls but not in Chinese boys. Another study performed in Chinese children also indicated that gender differences may exist in various obesity-related genes [23] . In our study, the reasons for the difference between the sexes may be as follows: 1) the adipose tissue distribution between women and men is quite different and 2) bone geometric structures vary between genders.…”