Common BMI and diabetes-related genetic variants: A pilot study among indigenous people in the Brazilian Amazon

Abstract This study was carried out to investigate the frequency of genetic variants related to body mass index (BMI) and type 2 diabetes (T2D) and evaluating the potential impact of risk alleles on susceptibility to these disorders in six indigenous peoples from Brazilian Amazon region. The majority of Fst values for pairwise population comparisons among the indigenous groups are low or moderate. The indigenous people show high values of differentiation with Africans, Europeans and Southeast Asians and moderate values with East Asian and American populations, as expected. The allelic frequencies among indigenous indicate that the majority of associations observed with T2D in continental populations can be replicated in native Amazonians. The genetic risk scores calculated for T2D in indigenous are high and similar to those calculated for Americans and East Asians, while the estimates obtained for obesity are low, probably due to the low frequencies of the risk allele of the FTO gene found in our samples. ADRB3-rs4994 and ABCC8-rs1799854 genes showed a significant association with BMI and waist circumference, and the KCNJ11-rs5219 gene with hyperglycemia. These results emphasize the importance of knowing the genetic variability underlying complex genetic diseases in indigenous peoples and the search for particular or rare variants.摘要 本研究旨在探究与身体质量指数（BMI）及2型糖尿病（T2D）相关的遗传变异发生频率，并评估风险等位基因对巴西亚马逊地区六个原住民群体罹患上述两种疾病的易感风险的潜在影响。在上述原住民群体间的两两群体比较中，多数群体分化系数（Fst）值处于较低或中等水平。如预期一致，该原住民群体与非洲、欧洲及东南亚人群的遗传分化程度较高，而与东亚人群及美洲人群的遗传分化程度处于中等水平。原住民群体的等位基因频率数据显示，在大陆人群中已观测到的与T2D相关的多数遗传关联，均可在亚马逊原住民群体中得到重复验证。针对原住民群体的T2D遗传风险评分较高，与美洲人群及东亚人群的评分结果相近；而针对肥胖的遗传风险评分则相对较低，这大概率缘于本研究样本中FTO基因风险等位基因的低携带频率。ADRB3-rs4994与ABCC8-rs1799854基因分别与BMI及腰围呈显著关联，KCNJ11-rs5219基因则与高血糖症存在显著相关性。上述研究结果凸显了探究原住民群体复杂遗传病背后的遗传变异多样性，并开展特异性或罕见变异搜寻工作的重要性。