Dyslexia Polygenic Scores Show Heightened Prediction of Verbal Working Memory and Arithmetic

Abstract

ABSTRACT Purpose The aim of this study is to establish which specific cognitive abilities are phenotypically related to reading skill in adolescence and determine whether this phenotypic correlation is explained by polygenetic overlap. Method In an Australian population sample of twins and non-twin siblings of European ancestry (734 ≤ N ≤ 1542 [50.7% < F < 66%], mean age = 16.7, range = 11–28 years) from the Brisbane Adolescent Twin Study, mixed-effects models were used to test the association between a dyslexia polygenic score (based on genome-wide association results from a study of 51,800 dyslexics versus >1 million controls) and quantitative cognitive measures. The variance in the cognitive measure explained by the polygenic score was compared to that explained by a reading difficulties phenotype (scores that were lower than 1.5 SD below the mean reading skill) to derive the proportion of the association due to genetic influences. Results The strongest phenotypic correlations were between poor reading and verbal tests ( R 2 up to 6.2%); visuo-spatial working memory was the only measure that did not show association with poor reading. Dyslexia polygenic scores could completely explain the phenotypic covariance between poor reading and most working memory tasks and were most predictive of performance on a test of arithmetic ( R 2 = 2.9 % ). Conclusion Shared genetic pathways are thus highlighted for the commonly found association between reading and mathematics abilities, and for the verbal short-term/working memory deficits often observed in dyslexia.