OBJECTIVE Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American, European, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans. RESEARCH DESIGN AND METHODS Using the PRSice software, ethnic-specific PRSs were computed with weights from the T2D GWAS multiancestry meta-analysis of 228,499 case and 1,178,783 control subjects. The South African Zulu study (n = 1,602 case and 981 control subjects) was used as the target data set. Validation and assessment of the best predictive PRS association with age at diagnosis were conducted in the Africa America Diabetes Mellitus (AADM) study (n = 2,148 case and 2,161 control subjects). RESULTS The discriminatory ability of the African American and multiethnic PRSs was similar. However, the African American–derived PRS was more transferable in all the countries represented in the AADM cohort and predictive of T2D in the country combined analysis compared with the European and multiethnic-derived scores. Notably, participants in the 10th decile of this PRS had a 3.63-fold greater risk (odds ratio 3.63; 95% CI 2.19–4.03; P = 2.79 × 10−17) per risk allele of developing diabetes and were diagnosed 2.6 years earlier than those in the first decile. CONCLUSIONS African American–derived PRS enhances polygenic prediction of T2D in continental Africans. Improved representation of non-European populations (including Africans) in GWAS promises to provide better tools for precision medicine interventions in T2D.

中文翻译：

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非洲 2 型糖尿病的多基因预测

非洲大陆人 2 型糖尿病 (T2D) 的多基因预测受到来自非洲的 T2D 的全基因组关联研究 (GWAS) 数量有限以及欧洲衍生的多基因风险评分 (PRS) 在不同种族中的可转移性差的不利影响. 我们着手评估非洲裔美国人、欧洲人或多民族衍生的 PRS 是否会改善非洲大陆人的多基因预测。研究设 南非祖鲁人研究（n = 1,602 例和 981 名对照受试者）被用作目标数据集。在非洲美洲糖尿病 (AADM) 研究（n = 2,148 例病例和 2,161 例对照组）中验证和评估了 PRS 与诊断年龄的最佳预测关联。结果 非裔美国人和多民族 PRS 的辨别能力相似。然而，与欧洲和多民族衍生的评分相比，非裔美国人衍生的 PRS 在 AADM 队列中代表的所有国家中更具可转移性，并且在国家综合分析中预测 T2D。值得注意的是，该 PRS 第 10 个十分位的参与者患糖尿病的每个风险等位基因的风险增加了 3.63 倍（优势比 3.63；95% CI 2.19-4.03；P = 2.79 × 10-17），并且被诊断出比 2.6 年前那些在第一个十分位数的。结论 非洲裔美国人衍生的 PRS 增强了非洲大陆人对 T2D 的多基因预测。在 GWAS 中提高非欧洲人群（包括非洲人）的代表性有望为 T2D 的精准医学干预提供更好的工具。