Genetic analysis of the RELN gene: Gender specific association with Alzheimer’s disease

Fehér, Ágnes; Juhász, Anna; Pákáski, Magdolna; Kálmán, János; Janka, Zoltán

doi:10.1016/j.psychres.2015.09.021

Cited by 25 publications

(16 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Taking RELN gene (coding reelin, an extracellular matrix glycoprotein) as an example, it participated in the regulation of neuronal migration, position, growth, and synaptic plasticity linking memory/learning formation, and it could prevent synaptic dysfunction induced by accumulation of Aβ deposits in AD . Some studies reported a significant association between RELN and AD among different populations . Another example could be DNMBP, which was a scaffold protein to bring dynamin and actin regulatory proteins together and participated in synaptic vesicle trafficking .…”

Section: Resultsmentioning

confidence: 99%

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

et al. 2018

View full text Add to dashboard Cite

The well-reproducible results showed the good performance of the combinatorial approach, and the remaining five new targets could be a good starting point for our understanding of the pathogenesis and drug discovery of AD. Moreover, this study supported validity of the combinatorial approach integrating ontology inference with network analysis in the discovery of novel drug target for neurological diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A few studies have assessed other genes or performed a systematic gene-by-sex genetic analysis. For example, female-or male-specific effects have been reported in ACE 16 , BDNF 17 and RELN 18 genes. Large-scale meta-analyses of genotyped data have largely focused on the AD affection status itself, rather than on sex-specific AD effects [19][20][21] .…”

mentioning

confidence: 99%

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Prokopenko

Hecker

Kirchner

et al. 2020

Sci Rep

View full text Add to dashboard Cite

With the advent of whole genome-sequencing (WGS) studies, family-based designs enable sex-specific analysis approaches that can be applied to only affected individuals; tests using family-based designs are attractive because they are completely robust against the effects of population substructure. These advantages make family-based association tests (FBATs) that use siblings as well as parents especially suited for the analysis of late-onset diseases such as Alzheimer's Disease (AD). However, the application of FBATs to assess sex-specific effects can require additional filtering steps, as sensitivity to sequencing errors is amplified in this type of analysis. Here, we illustrate the implementation of robust analysis approaches and additional filtering steps that can minimize the chances of false positive-findings due to sex-specific sequencing errors. We apply this approach to two family-based AD datasets and identify four novel loci (GRID1, RIOK3, MCPH1, ZBTB7C) showing sex-specific association with AD risk. Following stringent quality control filtering, the strongest candidate is ZBTB7C (P inter = 1.83 × 10 −7 ), in which the minor allele of rs1944572 confers increased risk for AD in females and protection in males. ZBTB7C encodes the Zinc Finger and BTB Domain Containing 7C, a transcriptional repressor of membrane metalloproteases (MMP). Members of this MMP family were implicated in AD neuropathology.Alzheimer's disease (AD) is the most common form of dementia worldwide, with a substantial burden for not only patients, but their families, society and the healthcare system. The impact of the disease is expected to increase further by 2050, with a projected 13.9 million Americans to develop AD or related dementias 1 . Like most complex diseases, AD is caused by a mixture of genetic and environmental factors. Early-onset familial AD (monogenic) is caused by rare fully penetrant mutations in APP, PSEN1, PSEN2 genes 2 . The more prevalent form, late-onset (sporadic) AD, is caused by a complex polygenic architecture, including large-effect variants in the APOE gene 3 . Environmental and lifestyle factors also affect the prevalence of the disease, however this domain is less well elucidated to date. Although one of the strongest predictors for AD is age, there are several other risk factors, including race 4 , high blood pressure 5 , brain trauma 6 and sex 7-10 .Not only are women at twofold greater risk than men, the progression of the disease and neurodegeneration is more rapid among women versus men 11,12 . In contrast, men with AD have higher mortality, as compared to women 12,13 . Interactions between sex and APOE ε4 have been previously reported. For instance, Altmann et al. showed that women have greater AD risk in the presence of APOE ε4, and this APOE-related risk in women may

show abstract

“…The effect of DME on brain processes has been understudied. Nevertheless, some, including CYP1A, Schizophrenia, autism spectrum disorder 90 and Alzheimer's disease 91,92 NP_059488 Neural tube defects 99,100 and schizophrenia 101,102 .…”

Section: Discussionmentioning

confidence: 99%

Exploratory Analysis of Rare and Novel Variants in Mexican Patients Diagnosed with Schizophrenia and Dementia

Martínez‐Magaña

Genis‐Mendoza

González-Covarrubias

et al. 2019

RIC

View full text Add to dashboard Cite

Background: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer's type (DAT) or SCZ. Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.

show abstract

Genetic analysis of the RELN gene: Gender specific association with Alzheimer’s disease

Cited by 25 publications

References 16 publications

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Exploratory Analysis of Rare and Novel Variants in Mexican Patients Diagnosed with Schizophrenia and Dementia

Contact Info

Product

Resources

About