FeatSNP: An Interactive Database for Brain-Specific Epigenetic Annotation of Human SNPs

Ma, Chunyu; Madden, Pamela; Gontarz, Paul; Wang, Ting; Zhang, Bo

doi:10.3389/fgene.2019.00262

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…Significantly associated SNPs following the regression analysis were functionally annotated using FeatSNP(Ma et al 2019) (http://featsnp.org) as previously described(Bhattacharyya et al 2020) (Supplementary Methods).…”

Section: Methodsmentioning

confidence: 99%

Genetic Variations in Evolutionary Accelerated Regions Disrupt Cognition in Schizophrenia

Bhattacharyya

Kukshal

Bhatia

et al. 2021

Preprint

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Cognition is believed to be a product of human evolution, while schizophrenia is ascribed as the by-product with cognitive impairment as it's genetically mediated endophenotype. Genomic loci associated with these traits are enriched with recent evolutionary markers such as Human accelerated regions (HARs). HARs are markedly different in humans since their divergence with chimpanzees and mostly regulate gene expression by binding to transcription factors and/or modulating chromatin interactions. We hypothesize that variants within HARs may alter such functions and thus contribute to disease pathogenesis. 49 systematically prioritized variants from 2737 genome-wide HARs were genotyped in a north-Indian schizophrenia cohort (331 cases, 235 controls). Six variants were significantly associated with cognitive impairment in schizophrenia, thirteen with general cognition in healthy individuals. These variants were mapped to 122 genes; predicted to alter 70 transcription factors binding sites and overlapped with promoters, enhancers and/or repressors. These genes and TFs are implicated in neurocognitive phenotypes, autism, schizophrenia and bipolar disorders; a few are targets of common or repurposable antipsychotics suggesting their draggability; and enriched for immune response and brain developmental pathways. Immune response has been more strongly targeted by natural selection during human evolution and has a prominent role in neurodevelopment. Thus, its disruption may have deleterious consequences for neuronal and cognitive functions. Importantly, among the 15 associated SNPs, 12 showed association in several independent GWASs of different neurocognitive functions. Further analysis of HARs may be valuable to understand their role in cognition biology and identify improved therapeutics for schizophrenia.

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Section: Methodsmentioning

confidence: 99%

Genetic Variations in Evolutionary Accelerated Regions Disrupt Cognition in Schizophrenia

Bhattacharyya

Kukshal

Bhatia

et al. 2021

Preprint

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“…The RegulomeDB probability score is ranging from 0 to 1, with 1 being the most likely to be a regulatory variant ( Boyle et al, 2012 ). Top-ranked SNPs (RegulomeDB score = 1) were further investigated using the GTEx portal ( Stanfill and Cao, 2021 ) and FeatSNP to assess their association with epigenetic effects in the human brain ( Ma et al, 2019 ). Additionally, SNPinfo, a web-based server, was used to detect SNPs with potential miRNA-binding sites ( Xu and Taylor, 2009 ).…”

Section: Methodsmentioning

confidence: 99%

“…Globally, more than 57.4 million adults live with dementia, and this number is estimated to increase to 152.8 million by 2050 (Nichols et al, 2022). Similarly, 537 million T2D patients, and this figure is expected to increase to 780 million (Magliano et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Decoding the genetic relationship between Alzheimer’s disease and type 2 diabetes: potential risk variants and future direction for North Africa

Boukhalfa,

Jmel,

Kheriji

et al. 2023

Front. Aging Neurosci.

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IntroductionAlzheimer’s disease (AD) and Type 2 diabetes (T2D) are both age-associated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies.Materials and methodsFirst, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants.ResultsA total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations.ConclusionOur study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers.

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“…In terms of genome functional annotation, rs34294852 is located within the 6 th intron of TNIP1 and downstream of the enhancer region GH05J151051 from GeneHancer 17,18 . Variant rs34294852 is predicted to alter the binding of the transcription factor MZF1 according to FeatSNP 19 , which is a database that aggregates brain-specific epigenetic data to examine the effects of genetic variants. In terms of expression quantitative trait loci (eQTL) data, variant rs34294852 is an eQTL for TNIP1 and GPX3 in blood, and it is also an eQTL for TNIP1 in monocytes and neutrophils and for GPX3 for neutrophils [20][21][22] .…”

Section: Mainmentioning

confidence: 99%

Post-GWAS multiomic functional investigation of theTNIP1locus in Alzheimer’s disease implicates mediation throughGPX3

Panyard

Reus

Ali

et al. 2022

Preprint

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FeatSNP: An Interactive Database for Brain-Specific Epigenetic Annotation of Human SNPs

Cited by 9 publications

References 26 publications

Genetic Variations in Evolutionary Accelerated Regions Disrupt Cognition in Schizophrenia

Genetic Variations in Evolutionary Accelerated Regions Disrupt Cognition in Schizophrenia

Decoding the genetic relationship between Alzheimer’s disease and type 2 diabetes: potential risk variants and future direction for North Africa

Post-GWAS multiomic functional investigation of theTNIP1locus in Alzheimer’s disease implicates mediation throughGPX3

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