Open Access Research

Associations of HLA alleles with specific language impairment

Ron Nudel1, Nuala H Simpson1, Gillian Baird2, Anne O’Hare3, Gina Conti-Ramsden4, Patrick F Bolton5, Elizabeth R Hennessy6, The SLI Consortium11, Anthony P Monaco17, Julian C Knight1, Bruce Winney8, Simon E Fisher109 and Dianne F Newbury1*

Author Affiliations

1 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK

2 Newcomen Centre, the Evelina Children’s Hospital, Westminster Bridge Road, London SE1 7EH, UK

3 Department of Reproductive and Developmental Sciences, University of Edinburgh, 20 Sylvan Place, Edinburgh EH9 1UW, UK

4 School of Psychological Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK

5 Departments of Child & Adolescent Psychiatry & Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK

6 University Child Health and DMDE, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZG, UK

7 Tufts University, Ballou Hall, Medford, MA 02155, USA

8 Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK

9 Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD, Nijmegen The Netherlands

10 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Geert Grooteplein-Noord, 6525 EZ, Nijmegen, The Netherlands

11 A list of SLIC members can be found in the acknowledgements section

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Journal of Neurodevelopmental Disorders 2014, 6:1  doi:10.1186/1866-1955-6-1

Published: 17 January 2014

Abstract

Background

Human 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.

Methods

We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types.

Results

Quantitative 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).

Conclusion

These 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.

Keywords:
Specific language impairment (SLI); HLA; Neurodevelopmental disorders; Genetic association