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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.[1]


  1. Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Conciatori, M., Stodgell, C.J., Hyman, S.L., O'Bara, M., Militerni, R., Bravaccio, C., Trillo, S., Montecchi, F., Schneider, C., Melmed, R., Elia, M., Crawford, L., Spence, S.J., Muscarella, L., Guarnieri, V., D'Agruma, L., Quattrone, A., Zelante, L., Rabinowitz, D., Pascucci, T., Puglisi-Allegra, S., Reichelt, K.L., Rodier, P.M., Persico, A.M. Biol. Psychiatry (2004) [Pubmed]
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