SLDB

Speech/Language Disorders Database

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Gene / phenotype associations for BDNF

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Entrez Id Symbol Location Disorder Brief Phenotype Reference Year Download
627 BDNF 11p13 SLI Reading and language impairment Simmons et al 2010 JSON | XML

Basic Study Type:  Linkage study

Study Cohort: 
Summary:

209 subjects from 4 families


Details:

"The data set is derived from Bartlett et al. [32] with minor changes to the original samples as noted below. The study sample was comprised of 1 nuclear and 3 extended Canadian families of Celtic ancestry (n = 158). Of these, 71 subjects had both phenotypic and genotypic information, 14 only DNA for genotypes and 1 only phenotypic information. The remaining subjects were required to fully reconstruct the pedigrees but do not have phenotypic or genotypic information. We have added 55 new subjects to the existing 4 families and removed the 1 nuclear family (n = 4 subjects) from analysis due to limited DNA availability. These numbers represent a change of 59 samples from the 2002 publication. These pedigrees were originally identified while recruiting for a linkage study of schizophrenia [102] and were noted to have a history of language or reading impairments.

"For inclusion in the study, the families were screened by a speech language pathologist via telephone interview for a history of language impairment segregating in the family. Those families with a strong family history of language impairment were scheduled for assessment. The largest family identified this way is only related to participants in the schizophrenia study by marriage (i.e., unrelated) and for the remaining families, no phenotypes from subjects with schizophrenia are used in any analysis. . .All subjects received a comprehensive battery administered by an experienced tester in their own homes [see 32 for more details].
". . .There were 10 subjects in the language-impaired-only group, 4 in the reading-impaired-only group and 15 in the language-impaired + reading-impaired group. In our sample, it was not necessary to exclude any subject from analysis because of mental retardation, abnormal hearing, oral motor or structural defects."

Genotyping Methods: 
"To further assess linkage to the 13q21 region, we genotyped 30 SNPs at roughly 0.3 cM interval across the 10 cM region. These SNPs were selected from HapMap [63] (Phase 3) requiring a minor allele frequency >0.4 and a linkage disequilibrium (LD) (R 2 ) < 0.2 as calculated from the CEPH (Utah residents with ancestry from northern and western Europe) HapMap samples, and at least 200 base pairs away from any (1) dbSNP (build 129) variant [64]; (2) repetitive element as identified by RepeatMasker (http://www.repeatmasker.org/); (3) repetitive elements identified by Tandem Repeats Finder (http://tandem.bu.edu/trf/trf.html), or (4) ‘structural variations’ listed in the UCSC genome browser [65] . From the candidates that met these criteria, final SNPs were chosen by walking down the chromosome in 0.3-cM intervals as determined by the Rutgers combined genetic map (for the list of chosen SNPs, see online suppl. table 2) [66] . Genotyping was performed by multiplex PCR of amplicons containing the chosen SNPs followed by the ligase detection reaction (LDR) method of Bruse et al. [67] on a Luminex 200 Multiplex Bio-Assay Analyzer. All samples were stored and handled as described previously [32] . Genotypes were called based on the same metric as in Bruse et al. [67], but initial clustering analysis was conducted by in-house Python 2.5.1 scripts using the scipy 0.6 library clustering routines (http://www.scipy.org/). This script automatically produces allele intensity plots color coded by called genotype. Markers with less than 85% completion were not considered further (n = 3). All plots were visually inspected (by T.R.S. and C.W.B.); SNPs that did not cluster appropriately were either dropped (n = 3) or called manually (n = 5)."

Analysis Methods: 
"First, we [used] a bivariate analysis of reading impairment in affected individuals jointly with language quantitative phenotypes in unaffected individuals. . .Second, we performed epistasis analysis using a functional coding variant in the brain-derived neurotrophic factor (BDNF) gene previously associated with reduced performance on working memory tasks."

Other Details: 
Diagnostic criteria:

Language impairment: SLQ on the TOLD of <= 85.
Reading impairment: Single non-word reading score (Word Attack) of one standard deviation below performance IQ.


Phenotypes for quantitative data:

Language: TOLD Speaking (expressive language measures), Grammar (syntax and morphology measures) and SLQ composite scores
Reading: Word ID, Word Attack and Pass Comp

Associated Markers:
rs6265 


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