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, SLI Consortium (includes Wendy Cohen), Wendy Cohen

Research output: Contribution to journalArticle

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Abstract

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

LanguageEnglish
Article number1
Number of pages9
JournalJournal of Neurodevelopmental Disorders
Volume6
Issue number1
DOIs
Publication statusPublished - 17 Jan 2014

Fingerprint

HLA Antigens
Language
Alleles
Aptitude
Single Nucleotide Polymorphism
Language Disorders
Population Control
Attention Deficit Disorder with Hyperactivity
Linguistics
Short-Term Memory

Keywords

  • specific language impairment
  • SLI
  • HLA
  • neurodevelopmental disorders
  • genetic association

Cite this

Nudel, R., Simpson, N. H., Baird, G., O'Hare, A., Conti-Ramsden, G., Bolton, P. F., ... SLI Consortium (includes Wendy Cohen) (2014). Associations of HLA alleles with specific language impairment. Journal of Neurodevelopmental Disorders, 6(1), [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. ; SLI Consortium (includes Wendy Cohen). / Associations of HLA alleles with specific language impairment. In: Journal of Neurodevelopmental Disorders. 2014 ; Vol. 6, No. 1.
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abstract = "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.  We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types.  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).  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.",
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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 & SLI Consortium (includes Wendy Cohen) 2014, 'Associations of HLA alleles with specific language impairment' Journal of Neurodevelopmental Disorders, vol. 6, no. 1, 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.; SLI Consortium (includes Wendy Cohen).

In: Journal of Neurodevelopmental Disorders, Vol. 6, No. 1, 1, 17.01.2014.

Research output: Contribution to journalArticle

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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 - SLI Consortium (includes Wendy Cohen)

AU - Cohen, Wendy

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N2 - 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.  We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types.  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).  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.

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KW - specific language impairment

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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). 1. https://doi.org/10.1186/1866-1955-6-1