Multiancestry Genome-Wide Association Study of Early Childhood Caries

作者：Poojan Shrestha, Mariaelisa Graff, Yu Gu, Ye Wang, C.L. Avery, Jeannie Ginnis, Miguel Simancas‐Pallares, Andréa G. Ferreira Zandoná, Rasha N. Alotaibi, Ekaterina Orlova, Hyeong Sik Ahn, Kim Nguyễn, H.M. Highland, Dan Lin, John S. Preisser, Gary D. Slade, Mary L. Marazita, Kari E. North, Kimon Divaris · 发表于：Journal of Dental Research · 年份：2024 · DOI：10.1177/00220345241291528 · 被引用次数：7 · 研究领域：Dental Health and Care Utilization、Child Nutrition and Water Access、Folate and B Vitamins Research

Early childhood caries (ECC) is the most common noncommunicable childhood disease—an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children ( N = 6,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI] = 0.42–0.79) among monozygotic twins and 0.44 (95% CI = 0.34–0.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci ( P < 5 × 10 −8 ) and 1 genome-wide significant gene ( TAAR6) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate...