@article{9155fff31e5f43818783fe4eb8975b6e,
title = "Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African-American youth",
abstract = "Background Rapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms. Objective To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach. Methods We conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African-American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted. Results Genome-wide significant effects were observed at rs1555839 (p=4.03×10 -8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer-promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule. Conclusion This study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene-brain-behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.",
keywords = "complex traits, epigenetics, genome-wide, psychiatry",
author = "{Pediatric, Imaging, Neurocognition, and Genetics Consortium} and Truong, {Dongnhu Thuy} and Adams, {Andrew Kenneth} and Steven Paniagua and Frijters, {Jan C.} and Richard Boada and Hill, {Dina E.} and Lovett, {Maureen W.} and Mahone, {E. Mark} and Willcutt, {Erik G.} and Maryanne Wolf and Defries, {John C.} and Alessandro Gialluisi and Clyde Francks and Fisher, {Simon E.} and Olson, {Richard K.} and Pennington, {Bruce F.} and Smith, {Shelley D.} and Joan Bosson-Heenan and Gruen, {Jeffrey R.}",
note = "Funding Information: The Genes, Reading, and Dyslexia study was funded by The Manton Foundation (JRG, JCF, JB-H, DTT). The Colorado Learning Disabilities Cohort was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Grant (P50HD027802; JRG, JCD, RKO, BFP, SDS, EGW). The Pediatric Imaging, Neurocognition, and Genetics study was funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (RC2DA029475). DTT was funded by the Lambert Family and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD07094 and K99HD094902). AKA was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007149). The Max Planck Society supported AG, CF and SEF, and funded the genetic analyses of the CLDRC cohort. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Funding the genes, reading, and Dyslexia study was funded by the Manton Foundation (Jrg, JcF, JB-H, Dtt). the colorado learning Disabilities cohort was funded by the eunice Kennedy Shriver national institute of child Health and Human Development national institutes of Health grant (P50HD027802; Jrg, JcD, rKO, BFP, SDS, egW). the Pediatric imaging, neurocognition, and genetics study was funded by the national institute on Drug abuse and the eunice Kennedy Shriver national institute of child Health and Human Development (rc2Da029475). Dtt was funded by the lambert Family and the eunice Kennedy Shriver national institute of child Health and Human Development (t32HD07094 and K99HD094902). aKa was funded by the eunice Kennedy Shriver national institute of child Health and Human Development (t32HD007149). the Max Planck Society supported ag, cF and SeF, and funded the genetic analyses of the clDrc cohort. the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019 Author(s).",
year = "2019",
month = aug,
day = "1",
doi = "10.1136/jmedgenet-2018-105874",
language = "English (US)",
volume = "56",
pages = "557--566",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "8",
}