Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious adverse drug reaction. We conducted a genomewide association study to search for genetic variants with a large effect size that increase the risk for BRONJ.Methods.We ascertained BRONJ cases according to the diagnostic criteria of the American Association of Oral and Maxillofacial Surgeons. We genotyped cases and a set of treatment-matched controls using Illumina Human Omni Express 12v1 chip (733,202 markers). To maximize the power of the study, we expanded the initial control set by including population and treatment-tolerant controls from publicly available sources. Imputation at the whole-genome level was performed to increase the number of single nucleotide polymorphisms (SNPs) investigated. Tests of association were carried out by logistic regression, adjusting for population structure. We also examined a list of candidate genes comprising genes potentially involved in the pathogenesis of BRONJ and genes related to drug absorption, distribution, metabolism, and excretion.
展开▼
机译：双膦酸盐相关的颌骨坏死（BRONJ）是一种严重的药物不良反应。我们进行了全基因组关联研究，以寻找具有较大影响范围的遗传变异，增加BRONJ的风险。方法。我们根据美国口腔颌面外科医师协会的诊断标准确定了BRONJ病例。我们使用Illumina Human Omni Express 12v1芯片（733,202个标记）对病例和一组与治疗匹配的对照进行基因分型。为了最大程度地发挥研究的作用，我们扩大了初始对照的范围，纳入了来自公开来源的人群和耐药性对照。进行全基因组水平的插补以增加所研究的单核苷酸多态性（SNP）的数量。关联检验通过逻辑回归进行，并调整了人口结构。我们还检查了候选基因的列表，这些候选基因包括可能与BRONJ的发病机理有关的基因以及与药物吸收，分布，代谢和排泄有关的基因。
展开▼
