Cleft lip/palate and educational attainment: cause, consequence or correlation? A Mendelian randomization study. (6th May 2020)

• Record Type: Journal Article
• Authors: Dardani, Christina; Howe, Laurence J; Mukhopadhyay, Nandita; Stergiakouli, Evie; Wren, Yvonne; Humphries, Kerry; Davies, Amy; Ho, Karen; Weinberg, Seth M; Marazita, Mary L; Mangold, Elisabeth; Ludwig, Kerstin U; Relton, Caroline L; Davey Smith, George; Lewis, Sarah J; Sandy, Jonathan; Davies, Neil M; Sharp, Gemma C
• Is Part Of: International journal of epidemiology. Volume 49:Number 4(2020)
• Page Start: 1282
• Page End: 1293
• Publication Date: 2020-05-06
• Subjects: Non-syndromic cleft -- educational attainment -- Mendelian randomization -- IQ -- orofacial cleft -- cleft lip and palate -- intelligence; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyaa047
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Background: Previous studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment. Methods: We performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence. Results: There was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) −0.05, 95% confidence interval (CI) −0.12 to 0.01, P 0.13; MR estimate (βMR) −0.002, 95% CI −0.009 to 0.006, P 0.679) or intelligence (rg −0.04, 95% CI −0.13 to 0.04, P 0.34; βMR −0.009, 95% CI −0.02 to 0.002, P 0.11). Conclusions: Common variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.