Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos.
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 × 10-8statistical 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.
1 Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Sanders
2 Department of Biostatistics, University of Washington, Seattle, WA, USA.
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Sofer
2 Department of Biostatistics, University of Washington, Seattle, WA, USA.
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Wong
2 Department of Biostatistics, University of Washington, Seattle, WA, USA.
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Kerr
3 Oral and Craniofacial Health Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Agler
4 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
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Shaffer
1 Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Beck
5 Department of Periodontology and Center for Oral and Systemic Diseases, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Offenbacher
6 Department of Epidemiology and Department of Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, New York City, NY, USA.
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Salazar
7 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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North
4 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.|8 Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|9 Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|10 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|11 Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
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Marazita
2 Department of Biostatistics, University of Washington, Seattle, WA, USA.
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CC
Laurie
12 Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Singer
13 Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Cai
14 Graduate School of Public Health, San Diego State University, San Diego, CA, USA.
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Finlayson
7 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|15 Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Divaris
D000293:Adolescent; D000328:Adult; D000368:Aged; D055113:Chronic Periodontitis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics* / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
epidemiology; genetics; genomics; observational study; periodontal attachment loss; survey and questionnaires