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      Associations of Six Single Nucleotide Polymorphisms in Obesity-Related Genes With BMI and Risk of Obesity in Chinese Children

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          Abstract

          OBJECTIVE

          Childhood obesity strongly predisposes to some adult diseases. Recently, genome-wide association (GWA) studies in Caucasians identified multiple single nucleotide polymorphisms (SNPs) associated with BMI and obesity. The associations of those SNPs with BMI and obesity among other ethnicities are not fully described, especially in children. Among those previously identified SNPs, we selected six (rs7138803, rs1805081, rs6499640, rs17782313, rs6265, and rs10938397, in or near obesity-related genes FAIM2, NPC1, FTO, MC4R, BDNF, and GNPDA2, respectively) because of the relatively high minor allele frequencies in Chinese individuals and tested the associations of the SNPs with BMI and obesity in Chinese children.

          RESEARCH DESIGN AND METHODS

          We investigated the associations of these SNPs with BMI and obesity in school-aged children. A total of 3,503 children participated in the study, including 1,229 obese, 655 overweight, and 1,619 normal-weight children (diagnosed by the Chinese age- and sex-specific BMI cutoffs).

          RESULTS

          After age and sex adjustment and correction for multiple testing, the SNPs rs17782313, rs6265, and rs10938397 were associated with BMI ( P = 1.0 × 10 −5, 0.038, and 0.00093, respectively) and also obesity ( P = 5.0 × 10 −6, 0.043, and 0.00085, respectively) in the Chinese children. The SNPs rs17782313 and rs10938397 were also significantly associated with waist circumference, waist-to-height ratio, and fat mass percentage.

          CONCLUSIONS

          Results of this study support obesity-related genes in adults as important genes for BMI variation in children and suggest that some SNPs identified by GWA studies in Caucasians also confer risk for obesity in Chinese children.

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          Most cited references 16

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          PLINK: a tool set for whole-genome association and population-based linkage analyses.

          Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.
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            Real time quantitative PCR.

            We have developed a novel "real time" quantitative PCR method. The method measures PCR product accumulation through a dual-labeled fluorogenic probe (i.e., TaqMan Probe). This method provides very accurate and reproducible quantitation of gene copies. Unlike other quantitative PCR methods, real-time PCR does not require post-PCR sample handling, preventing potential PCR product carry-over contamination and resulting in much faster and higher throughput assays. The real-time PCR method has a very large dynamic range of starting target molecule determination (at least five orders of magnitude). Real-time quantitative PCR is extremely accurate and less labor-intensive than current quantitative PCR methods.
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              Tracking of childhood overweight into adulthood: a systematic review of the literature.

              Overweight and obesity in youth are important public health concerns and are of particular interest because of possible long-term associations with adult weight status and morbidity. The aim of this study was to systematically review the literature and update evidence concerning persistence of childhood overweight. A computerized bibliographical search--restricted to studies with a prospective or retrospective longitudinal design--was conducted. Two authors independently extracted data and assessed the methodological quality of the included studies in four dimensions (i) study population and participation rate; (ii) study attrition; (iii) data collection and (iv) data analysis. Conclusions were based on a rating system of three levels of evidence. A total of 25 publications were selected for inclusion in this review. According to a methodological quality assessment, 13 studies were considered to be of high quality. The majority of these high-quality studies were published after 2001, indicating that recently published data, in particular, provide us with reliable information. All included studies consistently report an increased risk of overweight and obese youth becoming overweight adults, suggesting that the likelihood of persistence of overweight into adulthood is moderate for overweight and obese youth. However, predictive values varied considerably. Limiting aspects with respect to generalizability and methodological issues are discussed.
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                Author and article information

                Affiliations
                1Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China;
                2Laboratory of Human Genetics, Beijing Hypertension League Institute, Beijing, China;
                3Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
                Author notes
                Corresponding authors: Xingyu Wang, xingyuw@ 123456yahoo.com , and Jie Mi, jiemi2010@ 123456foxmail.com .

                L.W., B.X., and M.Z. contributed equally to this study.

                Journal
                Diabetes
                diabetes
                diabetes
                Diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                December 2010
                15 September 2010
                : 59
                : 12
                : 3085-3089
                2992769
                20843981
                0273
                10.2337/db10-0273
                © 2010 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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                Categories
                Obesity Studies

                Endocrinology & Diabetes

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