Exploring genetic markers of adult obesity risk in black adolescent South Africansthe Birth to Twenty Cohort

abstract: ...To date more than 90 loci that show an association with body mass index (BMI) and other obesity-related traits, have been discovered through genome-wide association studies. These findings have been widely replicated, mostly in European and Asian populations, but systematic investigation in African cohorts is still lacking. Therefore, the aim of our study was to replicate the association of six single-nucleotide polymorphisms (SNPs) previously linked to BMI, in a South African black adolescent cohort. The SNPs were in or near GNPDA2 (rs10938397), MTCH2 (rs10838738), NEGR1 (rs2568958), SH2B1 (rs7498665), STK33 (rs10769908) and TMEM18 (rs6548238). The SNPs were genotyped in 990 adolescents from the Birth to Twenty study, using an Illumina VeraCode assay, and association with BMI statistically assesed by using PLINK. Three of the SNPs tested were associated with BMI in this African cohort, and showed a consistent (albeit smaller) directional effect to that observed in non-African cohorts. We identified significant association between BMI and rs10938397 (effect allele-G) near GNPDA2 ( P adj =0.003), rs7498665 (effect allele-G) in SH2B1 ( P adj =0.014) and rs6548238 (effect allele-C) near TMEM18 ( P adj =0.030). This data suggests that common genetic variants potentially contributes to obesity risk in diverse population groups.

...) previously linked to BMI, in a South African black adolescent cohort. The SNPs were in or near GNPDA2 (rs10938397), MTCH2 (rs10838738), NEGR1 (rs2568958), SH2B1 (rs7498665), STK33 (rs10769908) and TMEM18 (rs6548238). The SNPs were genotyped in 990 adolescents from the Birth to Twenty study, using an Illumina VeraCode assay, and association with BMI statistically assesed by using PLINK. Three of the SNPs tested were associated with BMI in this African cohort, and showed a consistent (albeit smaller

...%) male adolescents, with a mean (s.d.) age of 13.70.2 years. Anthropometric measurements were obtained by using standard methods 13 and pubertal stage was assessed by using a validated self-assessment method. 14 SNPs previously associated with BMI 9 , 10 , 11 were selected for analysis, and include rs2568958 near NEGR1 , rs6548238 near TMEM18 , rs10938397 near GNPDA2 , rs10769908 in STK33 , rs10838738 in MTCH2 and rs7498665 in SH2B1 . Genotyping was performed using the GoldenGate VeraCode assay

... 1 Combined impact of risk alleles on average BMI in the Bt20 cohort. Risk alleles were summed for each individual. The number of individuals in each risk allele category is shown along the x axis. Table 1 Results of the six SNPs tested for association with log(BMI) in the Bt20 cohort Nearest gene SNP Chr N Alleles a P- values Effect b Other Frequency effect allele P unadj P adj c Effect size Beta d (s.e.m) GNPDA2 rs10938397 4 961 G A 0.21 0.002 0.003 0.013(0.004) MTCH2 rs10838738 11 982 G A

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SNP: rs10838738

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