Cleft lip/palate and educational attainment: cause, consequence, or correlation? A Mendelian randomization study

Importance Previous studies have found that children born with a non-syndromic form of cleft lip and/or palate have lower-than-average educational attainment. These differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as school absence, social stigmatization and impaired speech and language development), or confounding by the prenatal environment. A clearer understanding of this mechanism will inform development of interventions to improve educational attainment in individuals born with a cleft, which could have wide-ranging knock-on effects on their quality of life. Objective To assess evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment. Design Using summary data from genome-wide association studies (GWAS), we performed Linkage Disequilibrium (LD)-score regression and two-sample Mendelian randomization to evaluate the relationship between genetic liability to nsCL/P (GWAS n=3,987) and educational attainment (GWAS n=766,345), and intelligence (GWAS n=257,828). Results There was little evidence for shared genetic aetiology between nsCL/P and educational attainment (rg −0.03, 95% CI −0.14 to 0.08, P 0.58; βMR 0.002, 95% CI −0.001 to 0.005, P 0.417) or intelligence (rg −0.01, 95% CI −0.12 to 0.10, P 0.85; βMR 0.002, 95% CI −0.010 to 0.014, P 0.669). Conclusions and relevance Common genetic variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This information will help tailor clinical-, school-, social- and family-level interventions to improve educational attainment in this group. Question Do children born with a non-syndromic cleft lip with or without palate (nsCL/P) have lower-than average academic achievement because of an underlying genetic predisposition to educational attainment and/or intelligence? Findings There was little evidence for shared common variant genetic correlation between nsCL/P, educational attainment and intelligence. Meaning Common genetic variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This information will help tailor clinical-, school-, social- and family-level interventions to improve educational attainment in this group.