Genome-Wide Scan of Fifth Finger Clinodactyly

Fifth finger clinodactyly describes the conspicuous curvature of the fifth digit toward the other digits of the hand. Phenotypic expression can range from mild and almost imperceptible to severe, where function is impacted, and clinical intervention may be required. Although classically considered an autosomal dominant trait based on early family studies, no genes have been mapped for the trait. Further, there is epidemiological evidence that mild (typical-range) fifth finger clinodactyly may have a different etiology than more severe forms.

In this retrospective cross-sectional study, we carried out genome-wide association mapping of common genetic variants for clinodactyly in three cohorts separately and combined results via meta-analysis, treating the trait as either a continuous quantitative variable (n_meta = 631) or a binary outcome (n_meta = 1647).

The vast majority of participants in these cohorts exhibited mild forms of clinodactyly. Both the individual cohort results and meta-analyses revealed no genome-wide significant loci. We identified several possible suggestive signals (p < 1 × 10^-6), but these showed no evidence of replication.

While our results cannot definitively exclude the contribution of common variants to fifth finger clinodactyly due to the small sample size, they do suggest that the mild form of the trait is unlikely to be related to a major gene effect operating in a simple Mendelian manner.