Genome-Wide Studies of Specific Language Impairment

Abstract

Specific language impairment (SLI) is a multifactorial neurodevelopmental disorder which occurs unexpectedly and without an obvious cause. Over a decade of research suggests that SLI is highly heritable. Several genes and loci have already been implicated in SLI through linkage and targeted association methods. Recently, genome-wide association studies (GWAS) of SLI and language traits in the general population have been reported and, consequently, new candidate genes have been identified. This review aims to summarise the literature concerning genome-wide studies of SLI. In addition, this review highlights the methodologies that have been used to research the genetics of SLI to date, and also considers the current, and future, contributions that GWAS can offer.

Speech and Language: Translating the Genome

“…Despite these issues, clues into the genetic underpinnings of language-related phenotypes have emerged from classical linkage screens and targeted association studies (see reviews by [8][9][10]; Table 2). Several genomic loci that potentially harbor candidate genes have been Trends Identification of genes involved in language-related disorders, including speech apraxia, stuttering, specific language impairment, and developmental dyslexia, provides molecular gateways for investigating the neurobiology of unusual human traits.…”

“…Language: a structured system enabling the communication of thoughts, emotions, and concepts; involves the conventional use of arbitrary elements (spoken sounds, signs, or symbols), which are combined to form a potentially infinite mapped in family cohorts of developmental dyslexia (reading disability), specific language impairment (SLI), and stuttering. Common single-nucleotide polymorphisms (SNPs) on multiple chromosomes have been suggested to increase susceptibility to dyslexia and/or SLI, whereas rare single-nucleotide variants (SNVs) on chromosomes 12q23, 15q21, and 16p[ 4 1 7 _ T D $ D I F F ] 13 have been proposed as risk factors in stuttering [8,9,11]. Follow-up investigations of putative risk factors for association with affection status or quantitative measures of performance have yielded mixed findings, with many failures to replicate, and much of the heritability of language-related disorders remains unaccounted for [8,9].…”

“…Common single-nucleotide polymorphisms (SNPs) on multiple chromosomes have been suggested to increase susceptibility to dyslexia and/or SLI, whereas rare single-nucleotide variants (SNVs) on chromosomes 12q23, 15q21, and 16p[ 4 1 7 _ T D $ D I F F ] 13 have been proposed as risk factors in stuttering [8,9,11]. Follow-up investigations of putative risk factors for association with affection status or quantitative measures of performance have yielded mixed findings, with many failures to replicate, and much of the heritability of language-related disorders remains unaccounted for [8,9]. Together with improvements in molecular technologies, this is prompting a shift in strategies for identifying risk genes.…”

Genomic Imprinting As a Window into Human Language Evolution

“…While the behavioral effects of some imprinted genes are starting to be dissected in more detail, the phenotypic effects of many imprinted genes remain unclear, and thus it is not known what effect (if any) they may have on linguistic behavior. More generally, much still remains unknown about the genetic basis of linguistic behavior, and while it is known that certain aspects of the language phenotype are highly heritable, the currently known variants can only explain a small portion of this . Furthermore, the genome‐wide association studies often used to identify new variants rarely incorporate parent‐of‐origin effects that may be required to identify the contributions of imprinted genes, although there are exceptions .…”

“…More generally, much still remains unknown about the genetic basis of linguistic behavior, and while it is known that certain aspects of the language phenotype are highly heritable, [123] the currently known variants can only explain a small portion of this. [124,125] Furthermore, the genome-wide association studies often used to identify new variants rarely incorporate parent-of-origin effects that may be required to identify the contributions of imprinted genes, although there are exceptions. [74,75] With improved statistical methods to discern different parental effects in association studies, [79,89] this may prove a fruitful avenue for investigation.…”