Anderson Kerry, Cañadas-Garre Marisa, Chambers Robyn, Maxwell Alexander Peter, McKnight Amy Jayne
Epidemiology and Public Health Research Group, Centre for Public Health, Queen's University of Belfast, c/o Regional Genetics Centre, Belfast City Hospital, Belfast, United Kingdom.
Regional Nephrology Unit, Belfast City Hospital, Belfast, United Kingdom.
Front Genet. 2019 Sep 4;10:781. doi: 10.3389/fgene.2019.00781. eCollection 2019.
The role of chromosome Y in chronic kidney disease (CKD) remains unknown, as chromosome Y is typically excluded from genetic analysis in CKD. The complex, sex-specific presentation of CKD could be influenced by chromosome Y genetic variation, but there is limited published research available to confirm or reject this hypothesis. Although traditionally thought to be associated with male-specific disease, evidence linking chromosome Y genetic variation to common complex disorders highlights a potential gap in CKD research. Chromosome Y variation has been associated with cardiovascular disease, a condition closely linked to CKD and one with a very similar sexual dimorphism. Relatively few sources of genetic variation in chromosome Y have been examined in CKD. The association between chromosome Y aneuploidy and CKD has never been explored comprehensively, while analyses of microdeletions, copy number variation, and single-nucleotide polymorphisms in CKD have been largely limited to the autosomes or chromosome X. In many studies, it is unclear whether the analyses excluded chromosome Y or simply did not report negative results. Lack of imputation, poor cross-study comparability, and requirement for separate or additional analyses in comparison with autosomal chromosomes means that chromosome Y is under-investigated in the context of CKD. Limitations in genotyping arrays could be overcome through use of whole-chromosome sequencing of chromosome Y that may allow analysis of many different types of genetic variation across the chromosome to determine if chromosome Y genetic variation is associated with CKD.
Y染色体在慢性肾脏病（CKD）中的作用尚不清楚，因为在CKD的遗传分析中通常会排除Y染色体。CKD复杂的、性别特异性的表现可能受Y染色体遗传变异的影响，但现有已发表的研究有限，无法证实或反驳这一假设。尽管传统上认为Y染色体与男性特异性疾病有关，但将Y染色体遗传变异与常见复杂疾病联系起来的证据凸显了CKD研究中的一个潜在空白。Y染色体变异与心血管疾病有关，心血管疾病与CKD密切相关，且具有非常相似的性别二态性。在CKD中，对Y染色体上相对较少的遗传变异来源进行了研究。Y染色体非整倍体与CKD之间的关联从未得到全面探讨，而在CKD中对微缺失、拷贝数变异和单核苷酸多态性的分析在很大程度上限于常染色体或X染色体。在许多研究中，不清楚分析是否排除了Y染色体，或者只是没有报告阴性结果。与常染色体相比，缺乏归因、跨研究可比性差以及需要单独或额外分析意味着在CKD背景下对Y染色体的研究不足。通过使用Y染色体全染色体测序可以克服基因分型阵列的局限性，这可能允许分析整个染色体上许多不同类型的遗传变异，以确定Y染色体遗传变异是否与CKD相关。
