BACKGROUND AND AIMS: Genome-wide association studies (GWAS) have identified several loci that are associated with body mass index (BMI = kg/m(2)). However, little is known regarding whether the genetic basis of BMI differs among children of diverse racial/ethnic backgrounds, how the cumulative effect of these genes influences weight, or the contribution of these variants to body composition. This study examined the association between 17 GWAS-identified loci located in 16 genes and body-composition phenotypes in a multiethnic pediatric sample and evaluated the association of a composite genetic risk score with these phenotypes. METHODS: Anthropometric measures of BMI, waist circumference and waist-to-hip ratio were obtained in a sample of 298 children. Lean and fat mass were obtained from dual-energy X-ray absorptiometry (DXA). Genotypes of 17 single nucleotide polymorphisms (SNPs) were tested for association with the phenotypic measures, adjusted by standard covariates and estimates of genetic admixture. RESULTS: Both SNPs rs8050136 and rs9939609 in FTO were associated with BMI and waist circumference in a direction opposite to that observed among adults, and an inverse association was detected between the risk variant in MC4R and total lean body mass. Lean body mass mediated the association between TMEM18 and BMI. The association between the genetic risk score and body composition differed according to ethnic/racial classification. CONCLUSIONS: Our findings suggest that genetic associations with BMI among children are different from those in adults, that some loci may operate through lean body mass, and that genetic risk scores will not have universal applicability across ethnic/racial groups.
BACKGROUND AND AIMS: Genome-wide association studies (GWAS) have identified several loci that are associated with body mass index (BMI = kg/m(2)). However, little is known regarding whether the genetic basis of BMI differs among children of diverse racial/ethnic backgrounds, how the cumulative effect of these genes influences weight, or the contribution of these variants to body composition. This study examined the association between 17 GWAS-identified loci located in 16 genes and body-composition phenotypes in a multiethnic pediatric sample and evaluated the association of a composite genetic risk score with these phenotypes. METHODS: Anthropometric measures of BMI, waist circumference and waist-to-hip ratio were obtained in a sample of 298 children. Lean and fat mass were obtained from dual-energy X-ray absorptiometry (DXA). Genotypes of 17 single nucleotide polymorphisms (SNPs) were tested for association with the phenotypic measures, adjusted by standard covariates and estimates of genetic admixture. RESULTS: Both SNPs rs8050136 and rs9939609 in FTO were associated with BMI and waist circumference in a direction opposite to that observed among adults, and an inverse association was detected between the risk variant in MC4R and total lean body mass. Lean body mass mediated the association between TMEM18 and BMI. The association between the genetic risk score and body composition differed according to ethnic/racial classification. CONCLUSIONS: Our findings suggest that genetic associations with BMI among children are different from those in adults, that some loci may operate through lean body mass, and that genetic risk scores will not have universal applicability across ethnic/racial groups.
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Authors: Nancy L Heard-Costa; M Carola Zillikens; Keri L Monda; Asa Johansson; Tamara B Harris; Mao Fu; Talin Haritunians; Mary F Feitosa; Thor Aspelund; Gudny Eiriksdottir; Melissa Garcia; Lenore J Launer; Albert V Smith; Braxton D Mitchell; Patrick F McArdle; Alan R Shuldiner; Suzette J Bielinski; Eric Boerwinkle; Fred Brancati; Ellen W Demerath; James S Pankow; Alice M Arnold; Yii-Der Ida Chen; Nicole L Glazer; Barbara McKnight; Bruce M Psaty; Jerome I Rotter; Najaf Amin; Harry Campbell; Ulf Gyllensten; Cristian Pattaro; Peter P Pramstaller; Igor Rudan; Maksim Struchalin; Veronique Vitart; Xiaoyi Gao; Aldi Kraja; Michael A Province; Qunyuan Zhang; Larry D Atwood; Josée Dupuis; Joel N Hirschhorn; Cashell E Jaquish; Christopher J O'Donnell; Ramachandran S Vasan; Charles C White; Yurii S Aulchenko; Karol Estrada; Albert Hofman; Fernando Rivadeneira; André G Uitterlinden; Jacqueline C M Witteman; Ben A Oostra; Robert C Kaplan; Vilmundur Gudnason; Jeffrey R O'Connell; Ingrid B Borecki; Cornelia M van Duijn; L Adrienne Cupples; Caroline S Fox; Kari E North Journal: PLoS Genet Date: 2009-06-26 Impact factor: 5.917
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