Fine-tuning of Genome-Wide Polygenic Risk Scores and Prediction of Gestational Diabetes in South Asian Women
Fine-tuning of Genome-Wide Polygenic Risk Scores and Prediction of Gestational Diabetes in South Asian Women
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DOI：
10.1038/s41598-020-65360-y
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发表时间：
2020-06-02
影响因子：
4.6
通讯作者：
Anand, Sonia S.
中科院分区：
文献类型：
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作者：
Lamri, Amel;Mao, Shihong;Anand, Sonia S.
妊娠糖尿病（GDM）影响七分之一的新生儿，并与母亲和儿童的许多不良健康后果有关。GDM被怀疑与2型糖尿病（T2 D）有很大的共同遗传背景。我们研究的目的是描述不同的GDM多基因风险评分（PRS），并使用南亚出生队列（START）的数据测试其与GDM的相关性。使用修剪和阈值（P+T）、LDpred和GraBLD方法，从START中推导出832名南亚女性的PRS。体重来自DIAGRAM联盟的多种族和白色高加索人研究。GDM状态是通过口服葡萄糖耐量试验确定的南亚特定葡萄糖值。与GDM的相关性采用logistic回归进行检验。结果在英国生物银行（UKB）研究的南亚妇女中得到了复制。排名靠前的P+T、LDpred和GraBLD PRS均基于DIAGRAM的多种族研究。START（AUC=0.62，OR=1.60 [95% CI=1.44-1.69]）和UKB的南亚女性（AUC=0.65，OR=1.69 [95% CI=1.28-2.24]）中最佳PRS与GDM高度相关。我们的研究结果强调了将全基因组基因型和大型多种族研究的汇总统计相结合以优化南亚人PRS的重要性。
Gestational diabetes Mellitus (GDM) affects 1 in 7 births and is associated with numerous adverse health outcomes for both mother and child. GDM is suspected to share a large common genetic background with type 2 diabetes (T2D). The aim of our study was to characterize different GDM polygenic risk scores (PRSs) and test their association with GDM using data from the South Asian Birth Cohort (START). PRSs were derived for 832 South Asian women from START using the pruning and thresholding (P+T), LDpred, and GraBLD methods. Weights were derived from a multi-ethnic and a white Caucasian study of the DIAGRAM consortium. GDM status was defined using South Asian-specific glucose values in response to an oral glucose tolerance test. Association with GDM was tested using logistic regression. Results were replicated in South Asian women from the UK Biobank (UKB) study. The top ranking P+T, LDpred and GraBLD PRSs were all based on DIAGRAM's multi-ethnic study. The best PRS was highly associated with GDM in START (AUC=0.62, OR=1.60 [95% CI=1.44-1.69]), and in South Asian women from UKB (AUC=0.65, OR=1.69 [95% CI=1.28-2.24]). Our results highlight the importance of combining genome-wide genotypes and summary statistics from large multi-ethnic studies to optimize PRSs in South Asians.