1. Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos
- Author
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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, and Divaris, K
- Subjects
Biomedical and Clinical Sciences ,Dentistry ,Human Genome ,Dental/Oral and Craniofacial Disease ,Biotechnology ,Prevention ,Genetics ,Adolescent ,Adult ,Aged ,Chronic Periodontitis ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hispanic or Latino ,Humans ,Male ,Middle Aged ,Oligonucleotide Array Sequence Analysis ,Polymorphism ,Single Nucleotide ,Young Adult ,genetics ,periodontal attachment loss ,genomics ,epidemiology ,survey and questionnaires ,observational study - 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.
- Published
- 2017