RT Journal Article
SR Electronic
T1 Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African–American youth
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 557
OP 566
DO 10.1136/jmedgenet-2018-105874
VO 56
IS 8
A1 Dongnhu Thuy Truong
A1 Andrew Kenneth Adams
A1 Steven Paniagua
A1 Jan C Frijters
A1 Richard Boada
A1 Dina E Hill
A1 Maureen W Lovett
A1 E Mark Mahone
A1 Erik G Willcutt
A1 Maryanne Wolf
A1 John C Defries
A1 Alessandro Gialluisi
A1 Clyde Francks
A1 Simon E Fisher
A1 Richard K Olson
A1 Bruce F Pennington
A1 Shelley D Smith
A1 Joan Bosson-Heenan
A1 Jeffrey R Gruen
A1 ,
YR 2019
UL http://jmg.bmj.com/content/56/8/557.abstract
AB 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.