Genetic variation near ROBO1 is associated with craniofacial microsomia and related phenotypes in the Finnish population.

Craniofacial microsomia (CFM) encompasses a phenotypic continuum of congenital anomalies ranging from isolated microtia to more complex manifestations within the oculo-auriculo-vertebral spectrum, including Goldenhar syndrome, reflecting abnormal development of first and second pharyngeal arch-derived structures. While several genetic susceptibility loci have been reported, population-based evidence in individuals of European ancestry remains limited. Using nationwide data from FinnGen in the Finnish founder population, we identified a genome-wide significant association at a conserved intergenic locus near ROBO1, extending previous findings to a European ancestry cohort. The lead variant, rs62256696, lies within a regulatory region active in human embryonic craniofacial tissues during early development and shows concordant association with previously reported ROBO1 signals from non-European populations. Genetic correlation analyses demonstrated strong shared genetic architecture between CFM and auditory developmental phenotypes, consistent with the defined phenotypic continuum. Together, these findings extend previous observations to a new population context and support a role for regulatory variation at the ROBO1 locus in early craniofacial morphogenesis and auditory system development underlying craniofacial and auditory malformations.

82 European ancestry cases, 500,104 European ancestry controls