Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
Obesity (Silver Spring). 2019 May;27(5):845-854. doi: 10.1002/oby.22433. Epub 2019 Mar 18.
Meta-analyses of genome-wide association studies in Europeans have identified > 98 loci for BMI. Transferability of these established associations in Pima Indians was analyzed.
Among 98 lead single nucleotide polymorphisms (SNPs), 82 had minor allele frequency ≥ 0.01 in Pima Indians and were analyzed for association with the maximum BMI in adulthood (n = 3,491) and BMI z score in childhood (n = 1,958). Common tag SNPs across 98 loci were also analyzed for additional signals.
Among the lead SNPs, 13 (TMEM18, TCF7L2, MRPS33P4, PRKD1, ZFP64, FTO, TAL1, CALCR, GNPDA2, CREB1, LMX1B, ADCY9, NLRC3) were associated with BMI (P ≤ 0.05) in Pima adults. A multi-allelic genetic risk score (GRS), which summed the risk alleles for 82 lead SNPs, showed a significant trend for a positive relationship between GRS and BMI in adulthood (beta = 0.48% per risk allele; P = 1.6 × 10 ) and BMI z score in childhood (beta = 0.024 SD; P = 1.7 × 10 ). GRS was significantly associated with BMI across all age groups ≥ 5 years, except for those ≥ 50 years. The strongest association was seen in adolescence (age 14-16 years; P = 1.84 × 10 ).
In aggregate, European-derived lead SNPs had a notable effect on BMI in Pima Indians. Polygenic obesity in this population manifests strongly in childhood and adolescence and persists throughout much of adult life.
对欧洲人的全基因组关联研究进行的荟萃分析已经确定了超过 98 个与 BMI 相关的位点。分析了这些已建立的关联在皮马印第安人中的可转移性。
在 98 个先导单核苷酸多态性（SNP）中，有 82 个在皮马印第安人中的次要等位基因频率≥0.01，分析它们与成年时最大 BMI（n=3491）和儿童期 BMI z 分数（n=1958）的相关性。还分析了跨越 98 个位点的常见标签 SNP 以寻找额外的信号。
在先导 SNP 中，有 13 个（TMEM18、TCF7L2、MRPS33P4、PRKD1、ZFP64、FTO、TAL1、CALCR、GNPDA2、CREB1、LMX1B、ADCY9、NLRC3）与皮马成年人的 BMI 相关（P≤0.05）。多等位基因遗传风险评分（GRS）将 82 个先导 SNP 的风险等位基因相加，表明 GRS 与成年时 BMI 呈正相关的趋势具有统计学意义（每个风险等位基因增加 0.48%；P=1.6×10）和儿童期 BMI z 分数（β=0.024 SD；P=1.7×10）。GRS 与所有年龄组≥5 岁的 BMI 显著相关，除了年龄≥50 岁的人群。最强的关联出现在青春期（14-16 岁；P=1.84×10）。
总的来说，欧洲衍生的先导 SNP 对皮马印第安人的 BMI 有显著影响。该人群的多基因肥胖在儿童期和青春期表现明显，并在成年期的大部分时间持续存在。
