A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities

Evidence from two Italian independent samples

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
DOIs
Publication statusE-pub ahead of print - Apr 2017

Fingerprint

Aptitude
Language
Learning
Dyslexia
Reading
Learning Disorders
Genetic Models
Heterozygote
Alleles
Population
Brain
Single Nucleotide Polymorphism
Communication
Phenotype

Keywords

  • Association analysis
  • Developmental dyslexia
  • FOXP2
  • Language
  • Language-based learning disabilities

ASJC Scopus subject areas

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

@article{146bb8f2e6c141ce91b05e06ac069963,
title = "A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples",
abstract = "Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.",
keywords = "Association analysis, Developmental dyslexia, FOXP2, Language, Language-based learning disabilities",
author = "Alessandra Mozzi and Valentina Riva and Diego Forni and Manuela Sironi and Cecilia Marino and Massimo Molteni and Stefania Riva and Guerini, {Franca R.} and Mario Clerici and Rachele Cagliani and Sara Mascheretti",
year = "2017",
month = "4",
doi = "10.1002/ajmg.b.32546",
language = "English",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
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TY - JOUR

T1 - A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities

T2 - Evidence from two Italian independent samples

AU - Mozzi, Alessandra

AU - Riva, Valentina

AU - Forni, Diego

AU - Sironi, Manuela

AU - Marino, Cecilia

AU - Molteni, Massimo

AU - Riva, Stefania

AU - Guerini, Franca R.

AU - Clerici, Mario

AU - Cagliani, Rachele

AU - Mascheretti, Sara

PY - 2017/4

Y1 - 2017/4

N2 - Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.

AB - Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.

KW - Association analysis

KW - Developmental dyslexia

KW - FOXP2

KW - Language

KW - Language-based learning disabilities

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U2 - 10.1002/ajmg.b.32546

DO - 10.1002/ajmg.b.32546

M3 - Article

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

ER -