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

Christina Dardani*, Laurence J. Howe, Nandita Mukhopadhyay, Evie Stergiakouli, Yvonne Wren, Kerry Humphries, Amy Davies, Karen Ho, Seth M. Weinberg, Mary L. Marazita, Elisabeth Mangold, Kerstin U. Ludwig, Caroline L. Relton, George Davey Smith, Sarah J. Lewis, Jonathan Sandy, Neil M. Davies, Gemma C. Sharp

*Awdur cyfatebol y gwaith hwn

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

24 Dyfyniadau (Scopus)

Crynodeb

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.

Iaith wreiddiolSaesneg
Tudalennau (o-i)1282-1293
Nifer y tudalennau12
CyfnodolynInternational Journal of Epidemiology
Cyfrol49
Rhif cyhoeddi4
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 6 Mai 2020
Cyhoeddwyd yn allanolIe

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