Shared genetic loci between Alzheimer's disease and multiple sclerosis: Crossroads between neurodegeneration and immune system

Fominykh, Vera; Shadrin, Alexey; Jahołkowski, Piotr; Bahrami, Shahram; Athanasiu, Lavinia; Wightman, Douglas P; Uffelmann, Emil; Posthuma, Daniëlle; Selbæk, Geir; Dale, Anders M.; Djurovic, Srdjan; Frei, Oleksandr; Andreassen, Ole A.

doi:10.1016/j.nbd.2023.106174

Cited by 5 publications

(4 citation statements)

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“…However, even if it is not possible to discriminate whether herpesviruses are the cause or the effect of these diseases, the overlapping of pathogenetic pathways between virus infections and neurodegenerative and autoimmune processes constitutes a motivation to use antiviral therapies as treatment approach for these diseases. To date, in spite of promising results [ 244 , 245 ], few data are available on the efficacy of antiviral therapies.…”

Section: Discussionmentioning

confidence: 99%

“…A recognized important host-related factor is genetic background, supported by evidence of specific host genetic loci that increase the risk of the development of neurodegenerative or autoimmune diseases, such as the presence of APOE4, related to increased AD susceptibility [ 243 ]. Then, a recent study investigating the shared genetic susceptibility between AD and MS detected 16 shared loci, with 8 of them able to have concordant effects both on AD and MS [ 244 ]. These genes were involved in molecular signaling pathways related to inflammation and the structural organization of neurons.…”

Section: Relationship Between Herpesviruses Neurological Disorders An...mentioning

confidence: 99%

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Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

De Francesco

2024

Viruses

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Alzheimer’s disease and Parkinson’s disease represent the most common forms of cognitive impairment. Multiple sclerosis is a chronic inflammatory disease of the central nervous system responsible for severe disability. An aberrant immune response is the cause of myelin destruction that covers axons in the brain, spinal cord, and optic nerves. Systemic lupus erythematosus is an autoimmune disease characterized by alteration of B cell activation, while Sjögren’s syndrome is a heterogeneous autoimmune disease characterized by altered immune responses. The etiology of all these diseases is very complex, including an interrelationship between genetic factors, principally immune associated genes, and environmental factors such as infectious agents. However, neurodegenerative and autoimmune diseases share proinflammatory signatures and a perturbation of adaptive immunity that might be influenced by herpesviruses. Therefore, they might play a critical role in the disease pathogenesis. The aim of this review was to summarize the principal findings that link herpesviruses to both neurodegenerative and autoimmune diseases; moreover, briefly underlining the potential therapeutic approach of virus vaccination and antivirals.

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Section: Discussionmentioning

confidence: 99%

Section: Relationship Between Herpesviruses Neurological Disorders An...mentioning

confidence: 99%

Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

De Francesco

2024

Viruses

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“…LAVA, an integrated framework for local rg analysis that, in addition to testing the standard bivariate local rgs between two phenotypes, can further emphasize the relevance of mixed effects. [23] In this analysis, we used the LD reference panel based on 1000 Genomes phase 3 genotype data for European samples, and the genome is divided into 2495 partitioned semi-independent genomic regions, with an average size of 1 Mb. To study regions with apparent genetic relatedness, we estimated local genetic correlations using univariate LAVA to test for local genetic signals within each trait in 2,495 regions(P<1.00E-04 as threshold).…”

Section: Calculating Local Genetic Correlations and Emphasizing The R...mentioning

confidence: 99%

The shared genetic landscape of polycystic ovary syndrome and breast cancer: convergence on ER+ breast cancer but not ER- breast cancer

Bi,

Chen,

Zhao

et al. 2024

Preprint

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Background: The clinically high co-morbidity of polycystic ovary syndrome(PCOS) and breast cancer(BC) has been widely reported, but little is known about their shared genetic basis and mechanisms. Method: Using summary statistics from the largest GWASs to date, we performed a large-scale genome-wide cross-trait analysis of PCOS and BC with multiple genetic statistical methods to unlock potential shared genetic causes. Results: The study found some genetic overlap between the three trait pairs, and after dividing the entire genome into 2,495 independent regions, we observed chr8: 75,011,700- 76,295,483, and chr17: 6,305,079- 7,264,458 to be loci with significant localized genetic correlations. Pleiotropic analysis under a composite null hypothesis identified 1,183 significant potential pleiotropic SNPs in 3 trait pairs, FUMA mapped 26 pleiotropic loci in which 16q12.2 and 6q25.1were found to be duplicated across all three pairs of traits and then 3 colocalized loci detected by COLOC. The gene-based analysis identified 23 unique candidate pleiotropy genes, including the FTO locus shared by three trait pairs as well as SER1, RALB, and others. Whereas pathway enrichment analysis further highlighted the biological pathways present between PCOS-BCALL and PCOS-ERPBC that are primarily involved in prostate glandular acinus development, prostate glandular acinus morphogenesis and cellular response to stress. Latent Heritable Confounder Mendelian randomization (LHC-MR) further supports positive causality of PCOS in BCALL and ERPBC but not ERNBC. Conclusion: In conclusion our genome-wide cross-trait analysis identified a shared genetic basis between PCOS and BC, specific identical genetic mechanisms and causality between PCOS and various BC subtypes, which could better explains the genetics of the co-morbidity of PCOS and ERPBC rather than PCOS and ERNBC. These findings provide new insights into the biological mechanisms underlying the co-morbidity of these two complex diseases, which have important implications for clinical disease intervention, treatment, and improved prognosis.

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“…This is because their genetic risk architecture is generally based on common genetic variants with small effect sizes 19 . Fortunately, some novel genetic statisticians can solve this challenge by estimating the correlation of genetic structure between two complex diseases at multiple levels using GWAS summary statistics 20‐23 . These methods were employed to enhance the understanding of the shared genetic structure and causal relationships between Ps and IBD.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the gut‐skin axis: Common genetic structures in inflammatory bowel disease and psoriasis

Guo,

Luo,

et al. 2024

Skin Research and Technology

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BackgroundInflammatory bowel disease (IBD) and psoriasis (Ps) are common immune‐mediated diseases that exhibit clinical comorbidity, possibly due to a common genetic structure. However, the exact mechanism remains unknown.MethodsThe study population consisted of IBD and Ps genome‐wide association study (GWAS) data. Genetic correlations were first evaluated. Then, the overall evaluation employed LD score regression (LDSC), while the local assessment utilized heritability estimation from summary statistics (HESS). Causality assessment was conducted through two‐sample Mendelian randomization (2SMR), and genetic overlap analysis utilized the conditional false discovery rate/conjunctional FDR (cond/conjFDR) method. Finally, LDSC applied to specifically expressed genes (LDSC‐SEG) was performed at the tissue level. For IBD and Ps‐specific expressed genes, genetic correlation, causality, shared genetics, and trait‐specific associated tissues were methodically examined.ResultsAt the genomic level, both overall and local genetic correlations were found between IBD and Ps. MR analysis indicated a positive causal relationship between Ps and IBD. The conjFDR analysis with a threshold of < 0.01 identified 43 loci shared between IBD and Ps. Subsequent investigations into disease‐associated tissues indicated a close association of IBD and Ps with whole blood, lung, spleen, and EBV‐transformed lymphocytes.ConclusionThe current research offers a novel perspective on the association between IBD and Ps. It contributes to an enhanced comprehension of the genetic structure and mechanisms of comorbidities in both diseases.

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Shared genetic loci between Alzheimer's disease and multiple sclerosis: Crossroads between neurodegeneration and immune system

Cited by 5 publications

References 95 publications

Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?

The shared genetic landscape of polycystic ovary syndrome and breast cancer: convergence on ER+ breast cancer but not ER- breast cancer

Evidence for the gut‐skin axis: Common genetic structures in inflammatory bowel disease and psoriasis

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