基于家系的牙列Ⅰ类错合与裂隙的全基因组关联研究。
Family-based GWAS for dental class I malocclusion and clefts.
机构信息
Department of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA.
School of Dental Medicine, East Carolina University, Greenville, NC, 27834-4354, USA.
出版信息
BMC Oral Health. 2024 Jun 7;24(1):665. doi: 10.1186/s12903-024-04444-x.
BACKGROUND
Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts.
METHODS
Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion.
RESULTS
In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate.
CONCLUSIONS
These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.
背景
患有唇腭裂并定期接受矫正手术的个体，其中面部区域的生长会出现异常，导致前颌骨发育不全。然而，中面部区域的颅面形态也存在遗传因素，因此尽管这些个体表现出 III 类骨骼错颌，但他们的磨牙关系可能为 I 类。过去针对骨骼 II 类和 III 类错颌的全基因组关联研究（GWAS）表明，多个遗传标记通过多因子遗传模型对这些表型产生影响，但研究尚未检查与 I 类错颌相关的遗传标记。因此，我们的目标是进行一项基于家系的 GWAS，以鉴定与唇腭裂患者和非唇腭裂患者的磨牙关系定义的 I 类错颌相关的全基因组基因。
方法
我们的队列由 2006 年最初招募的 47 个菲律宾家庭的 739 名个体组成，旨在研究口面裂的遗传基础。所有个体均提供血液样本进行 DNA 提取和基因分型，并使用 5766 个单核苷酸多态性（SNP）定制面板进行分析。我们对有唇腭裂和无唇腭裂的参与者进行传递不平衡测试，以鉴定可能与 I 类错颌相关的遗传贡献者。
结果
在整个队列中，有 13 个 SNP 与关联达到基因组控制阈值（p<0.005），而在无唇腭裂的参与者队列中，有 5 个 SNP 与 I 类错颌相关，其中 4 个关联在整个队列中得到确认。SNP ABCA4 rs952499、SOX1-OT rs726455 和 RORA rs877228 的关联特别值得关注，因为过去的研究发现这些基因与各种颅面表型（包括唇腭裂）之间存在关联。
结论
这些发现支持 I 类错颌的多因子遗传模型，并表明不同颅面发育方面存在共同的遗传基础。
Zotero 插件