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Transforming growth factor alpha (TGFA) is a well-characterized mammalian growth factor. Since the first report of an association between DNA sequence variants at the TGFA genetic locus and nonsyndromic oral clefts, 47 studies have been carried out, producing conflicting results. In this review, the author synthesizes findings from published reports on the association between the TGFA gene and clefting in humans. Bias, lack of statistical power, and genuine population diversity can explain the diverse results. In the aggregate, TGFA is probably a genetic modifier of clefting in humans, which is consistent with the oligogenic model suggested for nonsyndromic oral clefts.