Genetic association of MPPED2 and ACTN2 with dental caries

B. O.C. Stanley; E. Feingold; M. Cooper; M. M. Vanyukov; B. S. Maher; R. L. Slayton; M. C. Willing; S. E. Reis; D. W. McNeil; R. J. Crout; R. J. Weyant; S. M. Levy; A. R. Vieira; M. L. Marazita; J. R. Shaffer

doi:10.1177/0022034514534688

Genetic association of MPPED2 and ACTN2 with dental caries

B. O.C. Stanley, E. Feingold, M. Cooper, M. M. Vanyukov, B. S. Maher, R. L. Slayton, M. C. Willing, S. E. Reis, D. W. McNeil, R. J. Crout, R. J. Weyant, S. M. Levy, A. R. Vieira, M. L. Marazita, J. R. Shaffer

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.

Original language	English (US)
Pages (from-to)	626-632
Number of pages	7
Journal	Journal of Dental Research
Volume	93
Issue number	7
DOIs	https://doi.org/10.1177/0022034514534688
State	Published - Jul 2014

Keywords

EDARADD
EPHA7
LPO
MTR
Single nucleotide polymorphism
ZMPSTE24

ASJC Scopus subject areas

General Dentistry

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10.1177/0022034514534688

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Stanley, B. O. C., Feingold, E., Cooper, M., Vanyukov, M. M., Maher, B. S., Slayton, R. L., Willing, M. C., Reis, S. E., McNeil, D. W., Crout, R. J., Weyant, R. J., Levy, S. M., Vieira, A. R., Marazita, M. L., & Shaffer, J. R. (2014). Genetic association of MPPED2 and ACTN2 with dental caries. Journal of Dental Research, 93(7), 626-632. https://doi.org/10.1177/0022034514534688

@article{74fc7caf0afd4377a6fc6c4b7a10076a,

title = "Genetic association of MPPED2 and ACTN2 with dental caries",

abstract = "The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.",

keywords = "EDARADD, EPHA7, LPO, MTR, Single nucleotide polymorphism, ZMPSTE24",

author = "Stanley, {B. O.C.} and E. Feingold and M. Cooper and Vanyukov, {M. M.} and Maher, {B. S.} and Slayton, {R. L.} and Willing, {M. C.} and Reis, {S. E.} and McNeil, {D. W.} and Crout, {R. J.} and Weyant, {R. J.} and Levy, {S. M.} and Vieira, {A. R.} and Marazita, {M. L.} and Shaffer, {J. R.}",

note = "Funding Information: This study was supported by the following National Institutes of Health grants: U01-DE018903 , R01-DE014899 , R01-DE009551 , R01-DE012101 , R01-DE018914 , P50-DA005605 , and R01-DA019157 , as well as the National Science Foundation / Department of Defense grant DBI-1263020 . The Dental Registry and DNA Repository is supported by the University of Pittsburgh School of Dental Medicine. The Dental SCORE sample is partially supported by the Commonwealth of Pennsylvania Department of Health grant ME-02-384 . ",

year = "2014",

month = jul,

doi = "10.1177/0022034514534688",

language = "English (US)",

volume = "93",

pages = "626--632",

journal = "Journal of Dental Research",

issn = "0022-0345",

publisher = "SAGE Publications Inc.",

number = "7",

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TY - JOUR

T1 - Genetic association of MPPED2 and ACTN2 with dental caries

AU - Stanley, B. O.C.

AU - Feingold, E.

AU - Cooper, M.

AU - Vanyukov, M. M.

AU - Maher, B. S.

AU - Slayton, R. L.

AU - Willing, M. C.

AU - Reis, S. E.

AU - McNeil, D. W.

AU - Crout, R. J.

AU - Weyant, R. J.

AU - Levy, S. M.

AU - Vieira, A. R.

AU - Marazita, M. L.

AU - Shaffer, J. R.

N1 - Funding Information: This study was supported by the following National Institutes of Health grants: U01-DE018903 , R01-DE014899 , R01-DE009551 , R01-DE012101 , R01-DE018914 , P50-DA005605 , and R01-DA019157 , as well as the National Science Foundation / Department of Defense grant DBI-1263020 . The Dental Registry and DNA Repository is supported by the University of Pittsburgh School of Dental Medicine. The Dental SCORE sample is partially supported by the Commonwealth of Pennsylvania Department of Health grant ME-02-384 .

PY - 2014/7

Y1 - 2014/7

N2 - The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.

AB - The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.

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KW - EPHA7

KW - LPO

KW - MTR

KW - Single nucleotide polymorphism

KW - ZMPSTE24

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Genetic association of MPPED2 and ACTN2 with dental caries

Abstract

Keywords

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