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

Research output: Contribution to journalArticle

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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 languageEnglish
Article number1
Number of pages9
JournalJournal of neurodevelopmental disorders
Volume6
DOIs
Publication statusPublished - 17 Jan 2014

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

Cite this

Nudel, R., Simpson, N. H., Baird, G., O'Hare, A., Conti-Ramsden, G., Bolton, P. F., ... The SLI Consortium (2014). Associations of HLA alleles with specific language impairment. Journal of neurodevelopmental disorders, 6, [1]. https://doi.org/10.1186/1866-1955-6-1

Associations of HLA alleles with specific language impairment. / Nudel, Ron; Simpson, Nuala H.; Baird, Gillian; O'Hare, Anne; Conti-Ramsden, Gina; Bolton, Patrick F.; Hennessy, Elizabeth R.; Monaco, Anthony P.; Knight, Julian C.; Winney, Bruce; Fisher, Simon E.; Newbury, Dianne F.; The SLI Consortium.

In: Journal of neurodevelopmental disorders, Vol. 6, 1, 17.01.2014.

Research output: Contribution to journalArticle

Nudel, R, Simpson, NH, Baird, G, O'Hare, A, Conti-Ramsden, G, Bolton, PF, Hennessy, ER, Monaco, AP, Knight, JC, Winney, B, Fisher, SE, Newbury, DF & The SLI Consortium 2014, 'Associations of HLA alleles with specific language impairment', Journal of neurodevelopmental disorders, vol. 6, 1. https://doi.org/10.1186/1866-1955-6-1
Nudel R, Simpson NH, Baird G, O'Hare A, Conti-Ramsden G, Bolton PF et al. Associations of HLA alleles with specific language impairment. Journal of neurodevelopmental disorders. 2014 Jan 17;6. 1. https://doi.org/10.1186/1866-1955-6-1
Nudel, Ron ; Simpson, Nuala H. ; Baird, Gillian ; O'Hare, Anne ; Conti-Ramsden, Gina ; Bolton, Patrick F. ; Hennessy, Elizabeth R. ; Monaco, Anthony P. ; Knight, Julian C. ; Winney, Bruce ; Fisher, Simon E. ; Newbury, Dianne F. ; The SLI Consortium. / Associations of HLA alleles with specific language impairment. In: Journal of neurodevelopmental disorders. 2014 ; Vol. 6.
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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.",
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.",
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TY - JOUR

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

VL - 6

JO - Journal of neurodevelopmental disorders

JF - Journal of neurodevelopmental disorders

SN - 1866-1947

M1 - 1

ER -