New insights from GWAS on longitudinal and cross-sectional BMI and related phenotypes in admixed children with Native American and European ancestries

Body-mass index (BMI) is a well-known marker of adiposity across all ages. The genetic architecture of BMI has been thoroughly studied among adults. In contrast, there are a few genome-wide association studies (GWAS) on children. Further, GWAS on children have been performed almost exclusively in Europeans at single ages. We aimed to better understand the genetic architecture of BMI trajectory across ages and how BMI is affected by Native American genetic ancestry. We performed cross-sectional and longitudinal GWAS for BMI-related traits on 904 admixed Chilean children with mostly European and Mapuche Native American genetic ancestry. We focused on BMI and two traits that occur at the minimum of the childhood BMI growth trajectory, namely, age at adiposity rebound (Age-AR) and BMI at adiposity rebound (BMI-AR). We found several variants in the immune gene HLA-DQB3 that are strongly associated with BMI at ages 1.5-2.5 years old, but not at other ages. We also identified a variant in the sex-determining gene DMRT1 significantly associated with Age-AR (P = 9.8 × 10−9). Further, BMI was significantly higher in Mapuche than in European children at all ages between 5.5 and 16.5 years old, but not before. Finally, Age-AR was significantly lower (P = 0.013) by 1.64 years in the Mapuche children compared with Europeans.

Reconstructed lost Native American populations from Eastern Brazil are shaped by differential Jê/Tupi ancestry

After the colonization of the Americas by Europeans and the consequent Trans-Atlantic Slave Trade, most Native American populations in eastern Brazil disappeared or went through an admixture process that configured a population composed of three main genetic components: the European, the sub-Saharan African and the Native American. The study of the Native American genetic history is challenged by the availability of genome-wide samples from Native American populations, the technical difficulties to develop ancient DNA studies and the low proportions of the Native American component in the admixed Brazilian populations (in average 7%). We analysed genome-wide data of 5,825 individuals from three locations of eastern Brazil: Salvador (North East), Bambui (South East), and Pelotas (South) and we reconstructed populations that emulate the Native American groups that were living in the 16th century around the sampling locations. This genetic reconstruction was performed after local ancestry analysis of the admixed Brazilian populations, through the rearrangement of the Native American haplotypes into reconstructed individuals with full Native American ancestry (51 reconstructed individuals in Salvador, 45 in Bambui and 197 in Pelotas). We compared the reconstructed populations with non-admixed Native American populations from other regions of Brazil through haplotype-based methods. Our results reveal a population structure shaped by the dichotomy of Tupi-/Jê- speaking ancestry related groups. We also show evidence of a decrease of the diversity of non-admixed Native American groups after the European contact, in contrast with the reconstructed populations, suggesting a reservoir of the Native American genetic diversity within the admixed Brazilian population.