Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide survey of large rare copy number variations in Alzheimer’s disease among Caribbean Hispanics

ABSTRACT: Recently genome-wide association studies have identified significant association between Alzheimer’s disease and variations in CLU, PICALM, BIN1, CR1, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7. However, the pathogenic variants in these loci have not yet been found. We conducted a genome-wide scan for large copy number variations (CNVs) in a dataset of Caribbean Hispanic origin (554 controls and 559 cases with late-onset Alzheimer’s disease) that was previously investigated in a SNP-based genome-wide association study using Illumina HumanHap 650Y platform. We ran four CNV calling algorithms and analyzed rare large CNVs (>100 Kb) to obtain high-confidence calls that were detected by at least two algorithms. In total, 734 such CNVs were observed in our dataset. Global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications, total or average CNV size; and number of genes affected by CNVs. However, we observed a nominal association between Alzheimer’s disease and a ~470 Kb duplication on chromosome15q11.2 (P=0.037). This duplication, encompassing up to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1 and WHAMML1) was present in 10 cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes was further confirmed by quantitative PCR. The current study did not detect CNVs (including common CNVs) that affect novel Alzheimer’s disease loci reported by large genome-wide association studies. However, since the array technology used in our study has limitations in detecting small CNVs, future studies must carefully assess novel AD associated genes for the presence of disease related CNVs. Case-control analysis, screening of large copy number variation in 559 Alzheimer cases and 554 control subjects of Caribbean Hispanic ancestry

ORGANISM(S): Homo sapiens

SUBMITTER: Ekaterina Rogaeva

PROVIDER: E-GEOD-33528 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Rehabilitation of Severe to Profound Sensorineural Hearing Loss in Adults: Audiological Outcomes.

Ciorba Andrea A Guidi Maria Paola MP Skarżyński Piotr H PH Bianchini Chiara C Rosignoli Monica M Mazzoli Manuela M Pelucchi Stefano S Hatzopoulos Stavros S

Ear, nose, & throat journal 20191215 3_suppl

The aim of this article is to describe the audiological patterns of 71 adult patients presenting severe to profound sensorineural hearing loss, who were rehabilitated by cochlear implants (CIs) and hearing aids. This is a retrospective study in a university setting, where the clinical records of 71 adult patients were reviewed and processed. Speech intelligibility was evaluated at one aided ear (CI) or at both aided ears (double CI or a combination of CI and hearing aid [HA]). Patients with a bi ...[more]

PMID: 31838921

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:Suicidal behavior (SB) has a complex etiology of genes, environment or both. One of the genetic components in SB could be copy number variations (CNVs), since CNVs are implicated in a range of neurodevelopmental disorders. However, a recently published genome-wide and case-control study failed to observe a significant role of CNVs in SB (see E-MTAB-3519). Here we complement those initial observations by conducting a brief CNV-association study, for the first time in a family-based trio-sample with severe suicide attempt (SA) outcome in offspring (n=660 trios; the \GISS\ sample, see http://www.ncbi.nlm.nih.gov/pubmed/23422793 and refs therein). For association testing, we here used the FBAT-CNV methodology (http://www.ncbi.nlm.nih.gov/pubmed/18228561), which allows for CNV association testing directly on the raw intensity values (Illumina \log R ratio\), evaluating any type of CNVs (e.g. de novo or inherited) without reliance on CNV calling algorithms and robust to control selection biases. Here we have deposited these raw logR-values for 88,450 on-chip CNV-loci of the HumanOmni1-Quad_v1 chip, arranged in a standard pedigree format used as input for FBAT-CNV analysis in SVS software (goldenhelix.com): column 1 is the family ID, column 2 is the Subject type (1 = offspring, 2 = mother, 3 = father), column 3 is the father ID (? for missing), column 4 is the mother ID (? for missing), column 5 is the sex (1 = female, 0 = male), column 6 is the affection status (1 = suicide attempt, 0 = not affected) and columns 7 and onward are the logR-values for each CNV-loci as is listed in the header row. We observed experiment-wide significant association (P ≤ 5.6 x 10-7) of two proximal CNVs at chromosome 14 (Illumina markers cnvi0108946 and cnvi0118308, with NCBI 36.3 start positions 22794779 and 22582820). However, these CNV-associations mapped to T-cell receptor regions, and therefore most likely reflect inter-individual variation in somatic rearrangements occurring in white blood cells (as our source of DNA was blood), rather than association with SA. In conclusion, our results did not suggest any major role of CNVs in SA etiology, in line with the results of the recent case-control study (see E-MTAB-3519).