Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos

A. E. Sanders, T. Sofer, Q. Wong, K. F. Kerr, C. Agler, J. R. Shaffer, J. D. Beck, S. Offenbacher, C. R. Salazar, K. E. North, M. L. Marazita, C. C. Laurie, R. H. Singer, J. Cai, T. L. Finlayson, K. Divaris

Research output: Contribution to journalArticle

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Abstract

Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus (TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association (P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American (n = 4,402) and African-American (n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level - a measure of lifetime periodontal tissue destruction - was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

LanguageEnglish (US)
Pages64-72
Number of pages9
JournalJournal of Dental Research
Volume96
Issue number1
DOIs
StatePublished - Jan 1 2017

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Chronic Periodontitis
Genome-Wide Association Study
Hispanic Americans
Health
African Americans
Genome
Gene Frequency
Single Nucleotide Polymorphism
Untranslated RNA
Genetic Markers
Mouth
Linear Models
Atherosclerosis
Population

Keywords

  • epidemiology
  • genetics
  • genomics
  • observational study
  • periodontal attachment loss
  • survey and questionnaires

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos. / Sanders, A. E.; Sofer, T.; Wong, Q.; Kerr, K. F.; Agler, C.; Shaffer, J. R.; Beck, J. D.; Offenbacher, S.; Salazar, C. R.; North, K. E.; Marazita, M. L.; Laurie, C. C.; Singer, R. H.; Cai, J.; Finlayson, T. L.; Divaris, K.

In: Journal of Dental Research, Vol. 96, No. 1, 01.01.2017, p. 64-72.

Research output: Contribution to journalArticle

Sanders, AE, Sofer, T, Wong, Q, Kerr, KF, Agler, C, Shaffer, JR, Beck, JD, Offenbacher, S, Salazar, CR, North, KE, Marazita, ML, Laurie, CC, Singer, RH, Cai, J, Finlayson, TL & Divaris, K 2017, 'Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos' Journal of Dental Research, vol 96, no. 1, pp. 64-72. DOI: 10.1177/0022034516664509
Sanders, A. E. ; Sofer, T. ; Wong, Q. ; Kerr, K. F. ; Agler, C. ; Shaffer, J. R. ; Beck, J. D. ; Offenbacher, S. ; Salazar, C. R. ; North, K. E. ; Marazita, M. L. ; Laurie, C. C. ; Singer, R. H. ; Cai, J. ; Finlayson, T. L. ; Divaris, K./ Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos. In: Journal of Dental Research. 2017 ; Vol. 96, No. 1. pp. 64-72
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