Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC

• Published in: Human genetics Vol. 136; no. 11-12; pp. 1395 - 1405
• Main Authors: Adams, Andrew K., Smith, Shelley D., Truong, Dongnhu T., Willcutt, Erik G., Olson, Richard K., DeFries, John C., Pennington, Bruce F., Gruen, Jeffrey R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2017; Springer; Springer Nature B.V
• Subjects: Alleles; Biomedical and Life Sciences; Biomedicine; Chromosome 7; Dyslexia - genetics; Filamins - genetics; Gene frequency; Gene Function; Genes; Genomes; Genomics; High-Throughput Nucleotide Sequencing; Human Genetics; Humans; Language; Learning disorders; Metabolic Diseases; Molecular Medicine; Mutation, Missense; Neoplasm Proteins - genetics; Nerve Tissue Proteins - genetics; Original Investigation; Reading
• ISSN: 0340-6717; 1432-1203; 1432-1203
• DOI: 10.1007/s00439-017-1838-z

Eleven loci with prior evidence for association with reading and language phenotypes were sequenced in 96 unrelated subjects with significant impairment in reading performance drawn from the Colorado Learning Disability Research Center collection. Out of 148 total individual missense variants identified, the chromosome 7 genes CCDC136 and FLNC contained 19. In addition, a region corresponding to the well-known DYX2 locus for RD contained 74 missense variants. Both allele sets were filtered for a minor allele frequency ≤0.01 and high Polyphen-2 scores. To determine if observations of these alleles are occurring more frequently in our cases than expected by chance in aggregate, counts from our sample were compared to the number of observations in the European subset of the 1000 Genomes Project using Fisher’s exact test. Significant P values were achieved for both CCDC136/FLNC ( P  = 0.0098) and the DYX2 locus ( P  = 0.012). Taken together, this evidence further supports the influence of these regions on reading performance. These results also support the influence of rare variants in reading disability.