Department of Developmental Biology, Stanford University Medical School, Stanford, CA.
Department Orthopaedic Surgery, Stanford University Medical Center, Stanford, CA.
Med Sci Sports Exerc. 2021 Apr 1;53(4):704-711. doi: 10.1249/MSS.0000000000002529.
This study aimed to screen the entire genome for genetic markers associated with risk for concussion.
A genome-wide association analyses was performed using data from the Kaiser Permanente Research Bank and the UK Biobank. Concussion cases were identified based on electronic health records from the Kaiser Permanente Research Bank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for concussion using a logistic regression model adjusting for sex, height, weight, and race/ethnicity using allele counts for single nucleotide polymorphisms. Previously identified genes within the literature were also tested for association with concussion.
There were a total of 4064 cases of concussion and 291,472 controls within the databases, with two single nucleotide polymorphisms demonstrating a genome-wide significant association with concussion. The first polymorphism, rs144663795 (P = 9.7 × 10-11; OR = 2.91 per allele copy), is located within the intron of SPATA5. Strong, deleterious mutations in SPATA5 cause intellectual disability, hearing loss, and vision loss. The second polymorphism, rs117985931 (P = 3.97 × 10-9; OR = 3.59 per allele copy), is located within PLXNA4. PLXNA4 plays a key role is axon outgrowth during neural development, and DNA variants in PLXNA4 are associated with risk for Alzheimer's disease. Previous investigations have identified five candidate genes that may be associated with concussion, but none showed a significant association in the current model (P < 0.05).
Two genetic markers were identified as potential risk factors for concussion and deserve further validation and investigation of molecular mechanisms.
本研究旨在筛选与脑震荡风险相关的全基因组遗传标记。
使用 Kaiser Permanente 研究银行和英国生物银行的数据进行全基因组关联分析。脑震荡病例是根据 Kaiser Permanente 研究银行和英国生物银行的电子健康记录从欧洲血统的个体中确定的。使用单核苷酸多态性的等位基因计数，通过逻辑回归模型调整性别、身高、体重和种族/民族，对两个队列的全基因组关联分析进行脑震荡测试。还测试了文献中先前确定的基因与脑震荡的相关性。
数据库中共有 4064 例脑震荡和 291472 例对照，有两个单核苷酸多态性与脑震荡具有全基因组显著相关性。第一个多态性 rs144663795（P=9.7×10-11；OR=2.91 个等位基因拷贝）位于 SPATA5 的内含子中。SPATA5 中的强有害突变会导致智力障碍、听力损失和视力损失。第二个多态性 rs117985931（P=3.97×10-9；OR=3.59 个等位基因拷贝）位于 PLXNA4 内。PLXNA4 在神经发育过程中轴突生长中起关键作用，PLXNA4 的 DNA 变体与阿尔茨海默病的风险相关。先前的研究已经确定了五个可能与脑震荡相关的候选基因，但在当前模型中没有一个显示出显著相关性（P<0.05）。
确定了两个遗传标记作为脑震荡的潜在危险因素，值得进一步验证和研究分子机制。
