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| 2. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 3. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 4. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 5. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 6. |
- Boisvert, Isabelle, et al.
(författare)
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Choice of Ear for Cochlear Implantation in Adults With Monaural Sound-Deprivation and Unilateral Hearing Aid
- 2012
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Ingår i: Otology and Neurotology. - : Lippincott, Williams and Wilkins. - 1531-7129 .- 1537-4505. ; 33:4, s. 572-579
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To identify whether speech recognition outcomes are influenced by the choice of ear for cochlear implantation in adults with bilateral hearing loss who use a hearing aid in 1 ear but have long-term auditory deprivation in the other. less thanbrgreater than less thanbrgreater thanStudy Design: Retrospective matched cohort study. Speech recognition results were examined in 30 adults with monaural sound deprivation. Fifteen received the implant in the sound-deprived ear and 15 in the aided ear. less thanbrgreater than less thanbrgreater thanSetting: Tertiary referral centers with active cochlear implant programs. less thanbrgreater than less thanbrgreater thanPatients: Adults with bilateral hearing loss and a minimum of 15 years of monaural sound deprivation who received a cochlear implant after meeting the traditional implantation criteria of the referral centers. less thanbrgreater than less thanbrgreater thanIntervention: Cochlear implantation with devices approved by the U.S. Food and Drug Administration. less thanbrgreater than less thanbrgreater thanMain Outcome Measure(s): Paired comparisons of postoperative monosyllabic word recognition scores obtained with the implant alone and in the usual listening condition (CI alone or bimodal). less thanbrgreater than less thanbrgreater thanResults: With the cochlear implant alone, individuals who received the implant in a sound-deprived ear obtained poorer scores than individuals who received the implant in the aided ear. There was no significant difference, however, in speech recognition results for the 2 groups when tested in their usual listening condition. In particular, poorer speech recognition scores were obtained with the cochlear implant alone by individuals using bimodal hearing. less thanbrgreater than less thanbrgreater thanConclusion: Similar clinical outcomes of cochlear implantation can be achieved by adults with a long-term monaural sound deprivation when comparing the usual listening condition, irrespective of whether the implant is in the sound-deprived or in the aided ear.
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| 7. |
- Boisvert, Isabelle, et al.
(författare)
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Long-Term Asymmetric Hearing Affects Cochlear Implantation Outcomes Differently in Adults with Pre- and Postlingual Hearing Loss
- 2015
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with post-lingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears.
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| 8. |
- Boisvert, Isabelle, et al.
(författare)
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Long-term monaural auditory deprivation and bilateral cochlear implants
- 2012
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Ingår i: NeuroReport. - : Lippincott, Williams and Wilkins. - 0959-4965 .- 1473-558X. ; 23:3, s. 195-199
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Tidskriftsartikel (refereegranskat)abstract
- Long-term binaural auditory deprivation is associated with poorer speech recognition outcomes after cochlear implantation, even for postlingual hearing loss. It is, however, unknown to what extent the outcomes of implantation are related to the peripheral changes occurring monaurally or to changes at a higher level in the auditory system related to binaural deafness. This retrospective study aimed to unravel peripheral and central contributions to cochlear implantation outcomes by comparing outcomes obtained in individual ears for adults with long-term monaural auditory deprivation (i.e. unilateral use of hearing aid) who received bilateral cochlear implants. Results showed that similar outcomes can be obtained with the implant placed in the auditory-deprived or in the aided ear. This suggests that the peripheral changes related to monaural auditory deprivation have little effect on outcomes of cochlear implantation. NeuroReport 23: 195-199
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| 9. |
- Boisvert, Isabelle, et al.
(författare)
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Monaural sound deprivation; opening a window on central processes underlying cochlear implantation outcomes
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- When considering unilateral cochlear implantation, clinicians must decide which ear should be implanted. This decision process is made more complex in the case of long-term monaural sound-deprivation where a hearing aid is used in the non-deprived ear. Clinical recommendations are not uniform where some clinicians suggest implanting the sound-deprived ear, regardless of the length of deprivation, to preserve the remaining hearing of the non-deprived ear. Others recommend implanting the non-deprived ear, arguing that implanting a recently stimulated ear provides higher outcomes with the implant. The literature discussing implanting the “better” or “worse” ear is inconclusive and none have specifically compared outcomes of implantation in ears with long-term monaural sound-deprivation.The current study draws its findings from cochlear implant centres located in 3 countries. Comparative analyses of cochlear implantation outcomes obtained in adults with monaural sound-deprivation of durations ranging from 15 to 65 years and implanted in the non-deprived (n≈90) or sound-deprived ear (n≈100) have been conducted. The results show that similar functional outcomes can be achieved by both groups when comparing the everyday listening condition (cochlear implant alone or bimodal hearing [i.e. cochlear implant in one ear and hearing aid in the other]). Moreover, higher outcomes were obtained after cochlear implantation by individuals with a long-term monaural sound-deprivation compared to individuals with a long-term bilateral sound-deprivation (n≈15), irrespective of which ear was implanted. These results pave the way to a discussion about central processes underlying cochlear implantation outcomes.
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| 10. |
- Boisvert, Isabelle, et al.
(författare)
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Relative Importance of Monaural Sound Deprivation and Bilateral Significant Hearing Loss in Predicting Cochlear Implantation Outcomes
- 2011
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Ingår i: Ear and Hearing. - : Lippincott, Williams and Wilkins. - 0196-0202 .- 1538-4667. ; 32:6, s. 758-766
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Making evidence-based recommendations to prospective unilateral cochlear implant recipients on the potential benefits of implanting one or the other ear is challenging for cochlear implant teams. This particularly occurs in cases where a hearing aid has only been used in one ear for many years (referred to here as the "hearing ear"), and the contralateral ear has, in essence, been sound-deprived. In such cases, research to date is inconclusive, and little anecdotal evidence exists to inform the debate and support best clinical practice. less thanbrgreater than less thanbrgreater thanDesign: Retrospective data on speech recognition outcomes of 16 adult participants who received a cochlear implant in an ear deprived of sound for a minimum of 15 yr were analyzed. All subjects were implanted through the Quebec Cochlear Implant Program and were provided with personalized intensive rehabilitation services. Data obtained from clinical records included demographic data and speech recognition scores measured after implantation with the sentences of a multimedia auditory test battery in the auditory-only condition. Speech recognition outcomes were compared with the duration of auditory deprivation in the implanted ear, bilateral significant hearing loss, and auditory stimulation before bilateral significant hearing loss. less thanbrgreater than less thanbrgreater thanResults: Using nonparametric correlation analyses, a strong negative correlation was demonstrated between speech recognition scores and the duration of bilateral significant hearing loss and with the duration of auditory stimulation before bilateral significant hearing loss. No significant correlation with the duration of auditory deprivation or with the duration of prior auditory stimulation in the implanted ear was found. less thanbrgreater than less thanbrgreater thanConclusions: These findings suggest that functional outcomes of cochlear implantation for unilateral sound deprivation may be more strongly influenced by central processes than peripheral effects stemming from the deprivation per se. This indicates the relevance of considering the clients history of binaural hearing rather than the hearing in each ear individually when discussing possible outcomes with a cochlear implant.
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