Associations of HLA alleles with specific language impairment

Ron Nudel,Elizabeth R Hennessy,Anthony P Monaco,Nuala H Simpson,Julian C Knight,Bruce Winney,Gina Conti-Ramsden,Simon E Fisher,Gillian Baird,Patrick F Bolton,Anne O’Hare,Dianne F Newbury

doi:10.1186/1866-1955-6-1

Abstract

BackgroundHuman leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment.MethodsWe perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types.ResultsQuantitative association analyses of imputed HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1 was associated with a measure of short-term memory (P = 0.004) and A3 with expressive language ability (P = 0.006). Parent-of-origin effects were found between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a negative correlation with receptive language ability when inherited from the mother (P = 0.021, P = 0.034, respectively) but are positively correlated with the same trait when paternally inherited (P = 0.013, P = 0.029, respectively). Finally, case control analyses using imputed HLA types indicated that the DR10 allele of HLA-DRB1 was more frequent in individuals with SLI than population controls (P = 0.004, relative risk = 2.575), as has been reported for individuals with attention deficit hyperactivity disorder (ADHD).ConclusionThese preliminary data provide an intriguing link to those described by previous studies of other neurodevelopmental disorders and suggest a possible role for HLA loci in language disorders.

Highlights

Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected
All SLI Consortium (SLIC) families were ascertained on the basis of a single proband with expressive and/or receptive language skills at least 1.5 standard deviations (SDs) below that expected for their age and Wechsler Intelligence Scale for Children (WISC) Perceptual Organization Index of more than 77.5 (1.5 SD below that expected for their age)
The results of this study suggest a potential involvement of HLA loci in specific language impairment (SLI)

Summary

Introduction

Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. Autoantibodies that react with brain tissue have been found in a relatively large number of children with an atypical variant of LandauKleffner syndrome and autism compared with controls Such antibodies were found in children affected by other neurological disorders, albeit less frequently [9]. Another study found antibodies that bound to rodent Purkinje cells in the serum of a mother with a child with specific language disorder, a child with autism, and a child with typical development. When this serum was injected in pregnant mice, the mouse pups had reduced exploratory behavior and impaired motor coordination [10]. The HLA region has been implicated in a linkage study of dyslexia [11]

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Conclusion