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Basic Science and Pathogenesis.

Alzheimers Dement

December 2024

Department of Genetics and Genomics, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India.

Background: Stroke, a cerebrovascular condition, and neurodegenerative diseases (ND) like Dementia, Multiple sclerosis, Parkinson's Disease, Amyotrophic Lateral Sclerosis are major types of neurological disorders, which are associated with increasing global morbidity and mortality burden. But to what extent shared genetic architecture is involved between stroke and ND is unknown.

Method: We investigated shared genetics between stroke (10 subtypes) and ND (6 diseases) using large scale Genome-Wide Association Study (GWAS) summary statistics data for Cross-Ancestry, European and South Asian samples including Indians.

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Background: ApoE4 is the strongest genetic risk factor for late onset Alzheimer's Disease (AD). However, ApoE4 has also been suggested to exhibit antagonistic pleiotropy, a phenomenon by which some allelic variations of a gene promote fitness during certain periods of life but may be detrimental in others. Previous work suggests that ApoE4 carriers exhibit superior performance on executive function tasks in early and middle age, while later in life (>70 years) ApoE4 carriers experience greater cognitive decline across multiple domains.

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Background: Myocardial infarction (MI) is a leading cause of death while those surviving MI are still at risk of developing dementias. Alzheimer's disease (AD) is the leading cause of dementia currently without a cure or an effective prevention even in vulnerable subpopulations. Both AD and MI are common causes of disabilities and deaths in aging populations.

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Background: Ovarian cancer is a lethal female cancer with a rising incidence that is often diagnosed late due to a lack of symptoms, affecting survival and quality of life. Studies suggest that dietary factors, especially the levels of branched-chain amino acids such as valine, may influence its development. While valine is essential for metabolism, its specific role in ovarian cancer remains unclear, necessitating further research.

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Objective: To investigate the potential causal relationship between type 1 diabetes mellitus (T1DM) and IgA nephropathy (IgAN) to deepen understanding of the association between these two conditions and to provide a scientific basis for future preventive and therapeutic strategies.

Methods: This study employed Mendelian randomization (MR) analysis, using single nucleotide polymorphisms (SNPs) derived from genome-wide association studies (GWAS) as genetic instrumental variables (IVs), to assess the association between T1DM and IgAN. The analytical approaches included univariable and multivariable MR, along with sensitivity analyses such as Mendelian randomization-Egger (MR-Egger) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), to evaluate the impact of heterogeneity and pleiotropy.

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