Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain

Schmidt‐Kastner, Rainald; Gülöksüz, Sinan; Kietzmann, Thomas; Os, Jim van; Rutten, Bart P. F.

doi:10.3389/fpsyt.2020.00393

Cited by 29 publications

(24 citation statements)

References 50 publications

(83 reference statements)

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“…Similarly, our genetic correlation results indicate that migraine was significantly correlated with mood swings, anxiety, depression, or neuroticism, consistent with a previous genetic correlation analysis study 50 . Thus, these findings suggest that migraine shares common variation risk with psychiatric disorders, such as schizophrenia, for which genome-wide significant loci involved in brain function have been reported 51,52 .…”

Section: Discussionmentioning

confidence: 66%

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

et al. 2021

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Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (CPS1, PBRM1, and SLC25A21) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.

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Section: Discussionmentioning

confidence: 66%

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

et al. 2021

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“…Another approach has been to examine if there was significant overlap between gene sets enriched for a particular RF and the GWAS variants implicated in schizophrenia. This has recently been done for genes related to ischaemia/hypoxia and the existing GWAS consortia data for schizophrenia and a significant enrichment was shown 49 . Variants within genes associated with schizophrenia interacting with ischaemia–hypoxia provide a specific starting point for functional and genomic studies related to obstetric complications.…”

Section: Investigating Interactions Between Genomic Variance and The mentioning

confidence: 99%

How do established developmental risk-factors for schizophrenia change the way the brain develops?

Eyles

2021

Transl Psychiatry

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The recognition that schizophrenia is a disorder of neurodevelopment is widely accepted. The original hypothesis was coined more than 30 years ago and the wealth of supportive epidemiologically data continues to grow. A number of proposals have been put forward to suggest how adverse early exposures in utero alter the way the adult brain functions, eventually producing the symptoms of schizophrenia. This of course is extremely difficult to study in developing human brains, so the bulk of what we know comes from animal models of such exposures. In this review, I will summarise the more salient features of how the major epidemiologically validated exposures change the way the brain is formed leading to abnormal function in ways that are informative for schizophrenia symptomology. Surprisingly few studies have examined brain ontogeny from embryo to adult in such models. However, where there is longitudinal data, various convergent mechanisms are beginning to emerge involving stress and immune pathways. There is also a surprisingly consistent alteration in how very early dopamine neurons develop in these models. Understanding how disparate epidemiologically-validated exposures may produce similar developmental brain abnormalities may unlock convergent early disease-related pathways/processes.

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“…Proposition 3 When J equals 2 and a is given, neighboring databases that satisfy the constraints (11) maximize the difference between the χ 2 values of tables D 1 and D 2 .…”

Section: Lemmamentioning

confidence: 99%

“…Although other methods for GWAS exist, a lot of recent research papers employ the chi-squared test for GWAS, such as [10][11][12][13], which were published in 2019 or 2020. Furthermore, the chi-squared test is used in numerous papers on GWAS to analyze COVID-19 [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Privacy-preserving chi-squared test of independence for small samples

Sei

Ohsuga

2021

BioData Mining

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Background The importance of privacy protection in analyses of personal data, such as genome-wide association studies (GWAS), has grown in recent years. GWAS focuses on identifying single-nucleotide polymorphisms (SNPs) associated with certain diseases such as cancer and diabetes, and the chi-squared (χ2) hypothesis test of independence can be utilized for this identification. However, recent studies have shown that publishing the results of χ2 tests of SNPs or personal data could lead to privacy violations. Several studies have proposed anonymization methods for χ2 testing with ε-differential privacy, which is the cryptographic community’s de facto privacy metric. However, existing methods can only be applied to 2×2 or 2×3 contingency tables, otherwise their accuracy is low for small numbers of samples. It is difficult to collect numerous high-sensitive samples in many cases such as COVID-19 analysis in its early propagation stage. Results We propose a novel anonymization method (RandChiDist), which anonymizes χ2 testing for small samples. We prove that RandChiDist satisfies differential privacy. We also experimentally evaluate its analysis using synthetic datasets and real two genomic datasets. RandChiDist achieved the least number of Type II errors among existing and baseline methods that can control the ratio of Type I errors. Conclusions We propose a new differentially private method, named RandChiDist, for anonymizing χ2 values for an I×J contingency table with a small number of samples. The experimental results show that RandChiDist outperforms existing methods for small numbers of samples.

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Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain

Abstract: genes related to synaptic functions were also related to ischemia-hypoxia. Variants of SCZ genes interacting with ischemia-hypoxia provide a specific starting point for functional and genomic studies related to OCs.

Cited by 29 publications

References 50 publications

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

How do established developmental risk-factors for schizophrenia change the way the brain develops?

Privacy-preserving chi-squared test of independence for small samples

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