Genetic-environmental Risk Factors for Tooth Agenesis: A Familial Case-control Study in China

Tooth agenesis (TA) is a common dental developmental anomaly influenced by genetic and environmental factors, though the specific contributions of these factors in large populations are not well understood. This study aimed to determine the genetic and environmental impact on TA and tooth development in a Chinese population.

We conducted a family-based case-control study involving 106 TA families (385 participants) and 197 controls (618 participants). Clinical examinations, evaluations of 25 potential risk factors, heritability and genetic analyses, including whole-exome sequencing and Sanger sequencing were performed.

106 TA probands exhibited 60.0% hypodontia and 34.0% oligodontia/anodontia, with 17% presenting systemic changes. TA heritability was estimated at 82.1%, higher in females than in males. Genetic contributions(heritability) decreased with increased environmental exposure (from 95.0% to 86.5%, P < .05). Identified genetic patterns in TA families included monogenic (54.05%), oligogenic (27.03%), and other patterns (18.92%). Key TA genes in TA families were WNT10A (63.3%), EDA (23.3%) and PAX9 (20.0%). WNT10A appeared in both monogenic and oligogenic patterns, and was also found in some unaffected familial controls. A family history increased offspring TA risk by 20-fold. Environmental contribution of TA was 17.9%, with unprotected electromagnetic radiation exposure (≥4 hours/d) during pregnancy increasing 4-fold risk.

Genetic contribution is more statistically significant in TA patients with more severe phenotypes, and in females. Heritability of TA declined with increased environmental exposure. Multiple genetic modes exist in TA families. Additionally, environmental factors, like unprotected electromagnetic radiation during pregnancy, are likley to play a role in TA development.