包括药物基因组学在内的精准医学是目前医学领域发展最快的方向。目前已有>100个药物的易感位点被应用到临床，用于个体化用药方案制定，以达到最好疗效和减少不良反应。但仍有大量药物基因组易感位点没有被定位，特别是中国人群特异位点的定位还需要大量原创新研究。化疗药物的药物适用范围窄，伴随大量的不良反应，常用的铂类化疗药物可导致肾毒性、耳毒性等多种不良反应，毒性较低的卡铂却能导致较多的骨髓抑制。由于没有基因组学的证据，目前在分子检验领域还没有开展针对性的药物基因组位点的检测，用于知道铂类药物的选择和剂量控制。我们已经对63个极端患者进行了全基因组测序，测序结果良好，但是由于样本量较小不能达到统计学要求，在本次研究中，我们将利用低覆盖度的全基因组测序检测另外150例极端不良反应患者基因型，并进行全基因组关联分析定位卡铂导致骨髓抑制的遗传易感位点，特别是卡铂的特异性位点，用于临床指导铂类药物的使用和监测

Precision medicine developed fast in medical field recently, with pharmacogenomics ranks the most part. pharmacogenomics variations has been recommended be to routinely checked for clinical applications for more than 100 drugs in clinical, guiding the personalized therapy to improve the outcomes as well as reducing adverse drug reactions (ADR). However, there are still lots of pharmacogenomics loci have not been determined, especially for Chinese specific variations. Chemotherapy drugs always have narrow index, resulting in a lot of ADRs. Platinum-based chemotherapy were widely used in cancer treatment, but with multiple common ADRs, such as nephrotoxicity, ototoxicity, and myelosuppression. Carboplatin has lower toxicity compared to cisplatin but with higher incidence of severe myelosuppression. No pharmacogenomics variation has been recommended to be detected in clinical laboratory to control the usage of carboplatin. We have investigated the genome information in 63 cases through whole genome-sequencing, and obtained good sequencing quality. However larger sample size is needed to increase the statistical power. In this study, we aim to screen out the genetic susceptibility loci for specific carboplatin-induced myelosuppression through low coverage whole genome sequencing based genome-wide association study with additional 150 cases, and hope to translate into clinic control of platinum treatment.