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全基因组关联研究揭示了多个与婴儿期乳牙发育相关的位点。

Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.

机构信息

Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom.

出版信息

PLoS Genet. 2010 Feb 26;6(2):e1000856. doi: 10.1371/journal.pgen.1000856.

DOI:10.1371/journal.pgen.1000856
PMID:20195514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2829062/
Abstract

Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5x10(-8), and 5 with suggestive association (P<5x10(-6)). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.

摘要

牙齿发育是一个高度遗传的过程，与其他生长和发育过程有关，并与整个颅面复合体的发育相互作用。牙齿发育异常很常见，牙缺失是人类最常见的发育异常。我们对来自 1966 年芬兰北部出生队列（NFBC1966）的 4564 人和来自阿冯纵向父母和儿童研究（ALSPAC）的 1518 人进行了一项关于首次出牙时间和一岁时牙齿数量的全基因组关联研究。我们在 P<5x10(-8) 处鉴定出 5 个位点，在 P<5x10(-6) 处鉴定出 5 个具有提示性关联的位点。这些位点包括几个与牙齿和其他器官发育有关的基因（KCNJ2、EDA、HOXB2、RAD51L1、IGF2BP1、HMGA2、MSRB3）。已确定的 4 个位点中的基因与癌症的发展有关。HOXB 基因簇内的一个变异与需要在 31 岁之前进行正畸治疗的咬合缺陷有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/d69cf254390f/pgen.1000856.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/f14b27695189/pgen.1000856.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/e2e42711e86d/pgen.1000856.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/d69cf254390f/pgen.1000856.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/f14b27695189/pgen.1000856.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/e2e42711e86d/pgen.1000856.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffd/2829062/d69cf254390f/pgen.1000856.g003.jpg

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[3]
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Mol Med. 2024-9-28

[4]
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[5]
The number of erupted teeth as a risk factor for dental caries in eighteen-month-old children: a cross‑sectional study.

BMC Oral Health. 2023-9-16

[6]
Skeletal Class II Malocclusion: From Clinical Treatment Strategies to the Roadmap in Identifying the Genetic Bases of Development in Humans with the Support of the Collaborative Cross Mouse Population.

J Clin Med. 2023-8-6

[7]
Development of Yorkshire Terrier Dentition.

Vet Sci. 2023-6-21

[8]
Preliminary study on genetic factors related to Demirjian's tooth age estimation method based on genome-wide association analysis.

Int J Legal Med. 2023-7

[9]
Integration of multimodal data in the developing tooth reveals candidate regulatory loci driving human odontogenic phenotypes.

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[10]
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本文引用的文献

[1]
Finding the missing heritability of complex diseases.

Nature. 2009-10-8

[2]
From ectodermal dysplasia to selective tooth agenesis.

Am J Med Genet A. 2009-9

[3]
A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).

Nat Genet. 2009-5

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Int J Biol Sci. 2009

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Nat Genet. 2009-3

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Nat Genet. 2009-1

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Nat Genet. 2008-5

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