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Evidence that disruption of Discoidin domain receptor 2 contributes to palate malformations through effects on the extracellular matrix.

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

Christina Dardani1, Laurence J Howe2,3, Nandita Mukhopadhyay4

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Genetic liability to non-syndromic orofacial clefts does not appear to cause lower educational attainment or intelligence. This finding helps understand the causes of academic challenges in individuals with clefts.

Keywords:
IQMendelian randomizationNon-syndromic cleftcleft lip and palateeducational attainmentintelligenceorofacial cleft

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Area of Science:

  • Genetics
  • Public Health
  • Developmental Biology

Background:

  • Children with non-syndromic orofacial clefts often have lower educational attainment.
  • Potential causes include genetic predisposition, cleft-related factors (stigma, speech issues), or prenatal environment.
  • Understanding these factors is crucial for interventions to improve quality of life.

Purpose of the Study:

  • To investigate if genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment.
  • To assess the genetic correlation and causal relationship between nsCL/P and educational outcomes.

Main Methods:

  • Genome-wide association study (GWAS) meta-analysis of nsCL/P cases and controls.
  • Linkage Disequilibrium (LD)-score regression to estimate genetic correlation with educational attainment and intelligence.
  • Two-sample Mendelian randomization to evaluate causal effects of nsCL/P liability.

Main Results:

  • Limited evidence for shared genetic etiology between nsCL/P and educational attainment (rg = -0.05, P = 0.13).
  • No significant causal relationship found between nsCL/P liability and educational attainment (βMR = -0.002, P = 0.679).
  • Similarly, no significant genetic correlation or causal link was observed with intelligence.

Conclusions:

  • Common genetic variants are unlikely to predispose individuals with nsCL/P to lower educational attainment or intelligence.
  • This study is a key step in understanding the etiology of educational attainment differences in this population.