Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
PLoS Genet. 2011 Sep;7(9):e1002275. doi: 10.1371/journal.pgen.1002275. Epub 2011 Sep 8.
The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P<5×10(-8) and were replicated in four independent study groups from the United States and Denmark with a total of 3,762 individuals; all combined P-values were below 10(-11). Two loci agreed with previous findings in primary tooth eruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9-4.1) fewer permanent teeth than children with 0 or 1 of these alleles.
恒牙萌出的顺序和时间被认为具有高度遗传性，对错颌畸形、拥挤和牙周病的风险有重要影响。我们对 5104 名丹麦国家出生队列的女性在 6 至 14 岁之间萌出的恒牙数量进行了全基因组关联研究，该研究分析了经过年龄调整的标准偏差评分，该评分是基于儿童时期的记录，通过多个时间点平均得出。四个位点在 P<5×10(-8)处显示出关联，并在来自美国和丹麦的四个独立研究组中得到了复制，共有 3762 人；所有综合 P 值均低于 10(-11)。其中两个位点与乳牙萌出的先前发现一致，分别与身高和乳腺癌有关。另外两个位点指向了基因组区域，这些区域以前没有任何具有显著全基因组关联研究结果的区域。ADK 基因内含子 SNP rs7924176 可能与单核细胞中的基因表达有关。四个遗传变异的综合效应在 10 至 12 岁之间最为明显，在这个年龄段，与具有 6 至 8 个延迟牙齿萌出等位基因的儿童相比，具有 0 或 1 个这些等位基因的儿童的恒牙数量平均少 3.5 个（95%置信区间：2.9-4.1）。
