Associations of HLA alleles with specific language impairment

Journal of Neurodevelopmental Disorders

Dianne F Newbury⁵  Simon E Fisher⁸  Bruce Winney¹  Julian C Knight⁵  Anthony P Monaco⁶  The SLI Consortium⁴  Elizabeth R Hennessy⁹  Patrick F Bolton⁷  Gina Conti-Ramsden²  Anne O’Hare³  Gillian Baird^1,10  Nuala H Simpson⁵  Ron Nudel⁵ 

[1] Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK;School of Psychological Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK;Department of Reproductive and Developmental Sciences, University of Edinburgh, 20 Sylvan Place, Edinburgh EH9 1UW, UK;A list of SLIC members can be found in the acknowledgements section;Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK;Tufts University, Ballou Hall, Medford, MA 02155, USA;Departments of Child & Adolescent Psychiatry & Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK;Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD, Nijmegen The Netherlands;University Child Health and DMDE, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZG, UK;Newcomen Centre, the Evelina Children’s Hospital, Westminster Bridge Road, London SE1 7EH, UK

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

Others  :  804582
DOI  :  10.1186/1866-1955-6-1

 received in 2013-10-14, accepted in 2014-01-02,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Nudel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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