Genome-wide Association Scan for Childhood Caries Implicates Novel Genes

被引:86
作者
Shaffer, J. R. [1 ]
Wang, X. [2 ]
Feingold, E. [1 ,3 ]
Lee, M. [2 ]
Begum, F. [3 ]
Weeks, D. E. [1 ,3 ]
Cuenco, K. T. [1 ,2 ]
Barmada, M. M. [1 ]
Wendell, S. K. [2 ]
Crosslin, D. R. [4 ]
Laurie, C. C. [4 ]
Doheny, K. F. [5 ]
Pugh, E. W. [5 ]
Zhang, Q. [4 ]
Feenstra, B. [6 ]
Geller, F. [6 ]
Boyd, H. A. [6 ]
Zhang, H. [6 ]
Melbye, M. [6 ]
Murray, J. C. [7 ]
Weyant, R. J. [8 ]
Crout, R. [9 ]
McNeil, D. W.
Levy, S. M. [10 ,11 ]
Slayton, R. L. [12 ]
Willing, M. C. [13 ]
Broffitt, B. [10 ]
Vieira, A. R. [2 ]
Marazita, M. L. [1 ,2 ]
机构
[1] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA 15219 USA
[3] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15219 USA
[4] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[5] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA
[6] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark
[7] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[8] Univ Pittsburgh, Sch Dent Med, Dept Dent Publ Hlth & Informat Management, Pittsburgh, PA 15219 USA
[9] W Virginia Univ, Sch Dent, Dept Periodont, Morgantown, WV 26506 USA
[10] Univ Iowa, Coll Dent, Dept Prevent & Community Dent, Iowa City, IA 52242 USA
[11] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA
[12] Univ Iowa, Coll Dent, Dept Pediat Dent, Iowa City, IA 52242 USA
[13] Washington Univ, Sch Med, Dept Pediat, Div Genet & Genom Med, St Louis, MO 63110 USA
关键词
caries; childhood caries; fluoride(s); genetics; genome-wide association study; genomics; DENTAL-CARIES; CLEFT-LIP; FLUORIDE INTAKE; POPULATION; EXPRESSION; CHILDREN; PALATE; LACTOPEROXIDASE; PREVALENCE; TUFTELIN;
D O I
10.1177/0022034511422910
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries.
引用
收藏
页码:1457 / 1462
页数:6
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