Evidence for shared genetic factors between myopia and intelligence in the Twins Early Development Study (TEDS)

Abstract

 

Purpose

 

Myopia has been consistently associated with intelligence (IQ), although the nature of this association is poorly understood. Both traits are heritable and common genetic variants have been associated with both in recent international genome wide association studies (GWAS). We sought to explore to what extent, if any, the genetic risk between IQ and myopia is shared using the twin model, and to ascertain how well refractive error variance is explained by genetic variants associated with IQ.

 

Methods

 

TEDS is a longitudinal birth cohort studied from a neurodevelopmental perspective using multivariate quantitative and molecular genetic techniques. IQ (g factor) was measured in 4661 twins (aged 16) and subjective refraction obtained from optometrists on 1996 twins (aged 16-18). A bivariate Cholesky decomposition model for IQ and spherical equivalent (SE) was constructed to assess the phenotypic variance and covariance attributable to genetic and environmental factors (adjusted for age and sex). Polygenic risk scores (PRS) for IQ were calculated for individual subjects using IQ GWAS meta-analysis results and Affymetrix 6.0 genotypes (HapMap phase II imputation, minor allele frequency >0.03, linkage disequilibrium pruning). The proportion of SE variance explained by IQ PRS was assessed using linear models adjusted for age and sex.

 

Results

 

The phenotypic correlation between SE and IQ was -0.14 (p<0.01) in 1154 twin subjects. In the bivariate twin model, 91% of the shared phenotypic correlation was explained by common genetic factors. The heritability of SE and IQ was 85% and 51% respectively, with 5.1% of the genetic factors for SE in common with those for IQ. Unique environmental factors contributed to 15% of SE variance, of which 3.5% were shared with IQ [Figure 1]. A higher IQ PRS was associated with a lower SE. The best-fit model to explain SE variation included 21,827 single nucleotide polymorphisms (at p≤0.1) and explained 2.8% of the variance (p=0.03).

 

Conclusions

 

This study has provided evidence for genetic pleiotropy between IQ and myopia, with shared genetic factors explaining 5% of SE heritability, and genetic variants for IQ explaining 2.8% of SE variation. Further research into how shared genetic factors result in myopia is required.  

 

Figure 1: Bivariate ACE model where A = additive genetic factors, C = common environmental factors and E = unique environmental factors