Buonaiuto Silvia, Marsico Franco, Mohammed Akram, Chinthala Lokesh K, Amos-Abanyie Ernestine K, Prins Pjotr, Mozhui Kyobeni, Rooney Robert J, Williams Robert W, Davis Robert L, Finkel Terri H, Brown Chester W, Colonna Vincenza
Dept of Genetics, Genomics and Informatics, UTHSC, USA.
Center for Biomedical Informatics, UTHSC, USA.
medRxiv. 2025 Feb 26:2025.01.03.25319944. doi: 10.1101/2025.01.03.25319944.
The Biorepository and Integrative Genomics (BIG) Initiative in Tennessee has developed a pioneering resource to address gaps in genomic research by linking genomic, phenotypic, and environmental data from a diverse Mid-South population, including underrepresented groups. We analyzed 13,152 exomes from BIG and found significant genetic diversity, with 50% of participants inferred to have non-European or several types of admixed ancestry. Ancestry within the BIG cohort is stratified, with distinct geographic and demographic patterns, as African ancestry is more common in urban areas, while European ancestry is more common in suburban regions. We observe ancestry-specific rates of novel genetic variants, which are enriched for functional or clinical relevance. Disease prevalence analysis linked ancestry and environmental factors, showing higher odds ratios for asthma and obesity in minority groups, particularly in the urban area. Finally, we observe discrepancies between self-reported race and genetic ancestry, with related individuals self-identifying in differing racial categories. These findings underscore the limitations of race as a biomedical variable. BIG has proven to be an effective model for community-centered precision medicine. We integrated genomics education, and fostered great trust among the contributing communities. Future goals include cohort expansion, and enhanced genomic analysis, to ensure equitable healthcare outcomes.
田纳西州的生物样本库与整合基因组学（BIG）计划开发了一种开创性资源，通过将来自包括代表性不足群体在内的中南地区多样化人群的基因组、表型和环境数据相联系，来填补基因组研究中的空白。我们分析了来自BIG的13152个外显子组，发现了显著的遗传多样性，50%的参与者被推断具有非欧洲或几种类型的混合血统。BIG队列中的血统是分层的，具有不同的地理和人口模式，非洲血统在城市地区更为常见，而欧洲血统在郊区更为常见。我们观察到了新遗传变异的血统特异性发生率，这些变异在功能或临床相关性方面更为丰富。疾病患病率分析将血统与环境因素联系起来，显示少数群体，特别是城市地区的少数群体患哮喘和肥胖症的比值比更高。最后，我们观察到自我报告的种族与遗传血统之间存在差异，相关个体在不同的种族类别中自我认同。这些发现强调了种族作为生物医学变量的局限性。BIG已被证明是社区中心精准医学的有效模式。我们整合了基因组学教育，并在参与社区之间建立了高度信任。未来的目标包括扩大队列规模和加强基因组分析，以确保公平的医疗保健结果。
