Introduction: Enamel hypoplasia causes a reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. Methods: A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7 to 82 years. Mixed models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Results: Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (p #x3c; 5 × 10^–8), and many suggestive association signals (5 × 10^–8 #x3c; p #x3c; 5 × 10^–6) near genes with plausible roles in tooth/enamel development. Conclusion: The strongest association signal (p = 1.57 × 10^–9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.
Hum Hered 2022;87:34–50

中文翻译：

---

多民族人群牙釉质发育不全的遗传分析

简介：牙釉质发育不全导致受影响的牙釉质厚度减少，是最常见的牙齿异常之一。这种缺陷是由干扰牙齿形成的环境和/或遗传因素引起的，强调了在流行病学和遗传水平上研究牙釉质发育不全的重要性。方法：在多个队列中进行釉质发育不全的全基因组关联，总共包括 7,159 名年龄在 7 到 82 岁之间的个体。混合模型用于测试遗传关联，同时考虑相关性和遗传种群结构。然后进行荟萃分析。在个体队列中测试了超过 500 万个单核苷酸多态性。结果：对个体队列的分析和荟萃分析确定了接近全基因组显着性的关联信号（p #x3c；5×10-8 ）和许多暗示性关联信号（5× 10-8# ^x3c；p#x3c；⁵ × 10 ^–6 ) 附近的基因在牙齿/牙釉质发育中具有合理的作用。结论：最强的关联信号 ( p = 1.57 × 10 ^–9 )在其中一个个体队列中的BMP2K附近被观察到。在荟萃分析中，在牙齿发育中具有合理作用的基因附近观察到额外的提示信号，例如SLC4A4这会影响牙釉质发育不全。需要更多的人类遗传学研究来复制这些结果，并且需要在模型系统中进行功能研究来验证我们的发现。
嗡嗡声 2022 年；87:34–50