Dental care–related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah’s Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment–specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.

与牙科护理相关的恐惧和焦虑 (DFA) 很普遍，影响口腔保健的利用，并与口腔健康状况不佳和生活质量下降有关。除了学习和文化因素外，遗传学被假设对 DFA 有贡献。因此，我们进行了全基因组关联研究，以确定有助于 DFA 的遗传变异。成人和青少年参与者来自 4 个队列（3 个来自美国阿巴拉契亚口腔健康研究中心，n = 1,144、1,164 和 535，以及英国雅芳父母和儿童纵向研究 [ALSPAC]，n= 2,078）。两种自我报告工具用于评估 DFA：牙科恐惧调查（美国队列）和 Corah 的牙科焦虑量表 (ALSPAC)。对 DFA 总分和子量表分数（回避、生理唤醒、对牙科治疗特定刺激的恐惧）进行了全基因组扫描，并根据年龄、性别、受教育程度、招募地点和遗传血统进行了调整。使用荟萃分析合并跨队列的结果。DFA 总分和子量表分数的遗传力估计值在不同队列中相似，范围从 23% 到 59%。荟萃分析揭示了基因位点与 2 个 DFA 分量表之间的3 个显着 ( P < 5E-8) 关联：生理唤醒和回避。附近的基因包括NTSR1 ( P = 3.05E-8), DMRTA1( P = 4.40E-8) 和FAM84A ( P = 7.72E-9)。其中，与回避分量表相关的NTSR1介导神经降压素功能，其缺陷可能导致小鼠的恐惧记忆改变。基因富集分析表明，与 DFA 总分和生理觉醒子量表得分相关的位点因与严重和持续性心理健康（例如，精神分裂症）和神经认知（例如，自闭症）障碍相关的基因而富集。遗传力分析表明 DFA 部分由遗传因素解释，我们的关联结果表明与其他心理状况有共同的遗传基础。