Associations of HLA alleles with specific language impairment

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

doi:10.1186/1866-1955-6-1

Associations of HLA alleles with specific language impairment

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

^*Corresponding author for this work

Medical Education

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	1
Number of pages	9
Journal	Journal of neurodevelopmental disorders
Volume	6
DOIs	https://doi.org/10.1186/1866-1955-6-1
Publication status	Published - 17 Jan 2014

Bibliographical note

Accepted: 2 January 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Funding

We would like to thank all the families, professionals, and individuals who participated in this research. In particular, we would like to thank Simon Fiddy for his assistance with data transformation and Benjamin Fairfax for the use of the Oxfordshire Control samples. DN is a Medical Research Council (MRC) Career Development Fellow and a Junior Research Fellow at St John's College, University of Oxford. The work of the DN lab is funded by the MRC (G1000569/1 and MR/J003719/1). RN is funded by a University of Oxford Nuffield Department of Medicine Prize Studentship. The genotyping of samples was funded by the Max Planck Society. The collection of the SLIC samples was supported by the Wellcome Trust (060774 and 076566). Recruitment of controls for the Oxfordshire study of gene expression in primary immune cells was supported by the Wellcome Trust (074318 and 088891), the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) (281824), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. Recruitment of controls for the POBI study was supported by the Wellcome Trust (072974, 088262). PFB is supported by an NIHR (UK) Senior Investigator award and the Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London. The work of the Wellcome Trust Centre in Oxford is supported by the Wellcome Trust (090532/Z/09/Z). We are very grateful to the other members of the SLIC for their contributions to this work: V. Slonims (Newcomen Centre, Evelina Children's Hospital, London), A. Clark, J. Watson (Speech and Hearing Sciences, Queen Margaret University, Edinburgh, UK), E. Simonoff, A Pickles (King's College London, Institute of Psychiatry); A. Everitt (University Child Health and DMDE, University of Aberdeen); J. Seckl (Molecular Medicine Centre, University of Edinburgh); H. Cowie (Department of Speech and Language Therapy, Royal Hospital for Sick Children, Edinburgh); W. Cohen (Psychological Sciences and Health, University of Strathclyde); J. Nasir (Division of Biomedical Sciences, St George's University of London); D. V. M. Bishop (Department of Experimental Psychology, University of Oxford); Z. Simkin (School of Psychological Sciences, University of Manchester).

Keywords

specific language impairment (SLI)
HLA
neurodevelopmental disorders
genetic association
false discovery rate
short-term-memory
disease associations
nonword repetititon
gene-expression
autism
linkage
locus
disorder
schizophrenia

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10.1186/1866-1955-6-1

Associations of HLA alleles with specific language
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 363 KB

Cite this

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title = "Associations of HLA alleles with specific language impairment",

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, false discovery rate, short-term-memory, disease associations, nonword repetititon, gene-expression, autism, linkage, locus, disorder, schizophrenia",

author = "Ron Nudel and Simpson, \{Nuala H.\} and Gillian Baird and Anne O'Hare and Gina Conti-Ramsden and Bolton, \{Patrick F.\} and Hennessy, \{Elizabeth R.\} and Monaco, \{Anthony P.\} and Knight, \{Julian C.\} and Bruce Winney and Fisher, \{Simon E.\} and Newbury, \{Dianne F.\} and \{The SLI Consortium\}",

note = "Accepted: 2 January 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.",

year = "2014",

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doi = "10.1186/1866-1955-6-1",

language = "English",

volume = "6",

journal = "Journal of neurodevelopmental disorders",

issn = "1866-1947",

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T1 - Associations of HLA alleles with specific language impairment

AU - Nudel, Ron

AU - Simpson, Nuala H.

AU - Baird, Gillian

AU - O'Hare, Anne

AU - Conti-Ramsden, Gina

AU - Bolton, Patrick F.

AU - Hennessy, Elizabeth R.

AU - Monaco, Anthony P.

AU - Knight, Julian C.

AU - Winney, Bruce

AU - Fisher, Simon E.

AU - Newbury, Dianne F.

AU - The SLI Consortium

N1 - Accepted: 2 January 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

PY - 2014/1/17

Y1 - 2014/1/17

N2 - 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.

AB - 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.

KW - specific language impairment (SLI)

KW - HLA

KW - neurodevelopmental disorders

KW - genetic association

KW - false discovery rate

KW - short-term-memory

KW - disease associations

KW - nonword repetititon

KW - gene-expression

KW - autism

KW - linkage

KW - locus

KW - disorder

KW - schizophrenia

U2 - 10.1186/1866-1955-6-1

DO - 10.1186/1866-1955-6-1

M3 - Article

SN - 1866-1947

VL - 6

JO - Journal of neurodevelopmental disorders

JF - Journal of neurodevelopmental disorders

M1 - 1

ER -

Associations of HLA alleles with specific language impairment

Abstract

Bibliographical note

Funding

Keywords

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