scholarly journals Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

2017 ◽  
Vol 136 (10) ◽  
pp. 1341-1351 ◽  
Author(s):  
Yen-Chen Anne Feng ◽  
◽  
Kelly Cho ◽  
Sara Lindstrom ◽  
Peter Kraft ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Relationship ◽  
Summary Statistics

scholarly journals NIAGADS Alzheimer’s GenomicsDB: A resource for exploring Alzheimer’s Disease genetic and genomic knowledge

2020 ◽  
Author(s):  
Emily Greenfest-Allen ◽  
Conor Klamann ◽  
Prabhakaran Gangadharan ◽  
Amanda Kuzma ◽  
Yuk Yee Leung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Real Time ◽  
Data Repository ◽  
Sequencing Analysis ◽  
Summary Statistics ◽  
Time Data ◽  
Report Generation ◽  
Sequencing Project ◽  
Gene Annotations

AbstractINTRODUCTIONThe NIAGADS Alzheimer’s Genomics Database is an interactive knowledgebase for AD genetics that provides access to GWAS summary statistics datasets deposited at NIAGADS, a national genetics data repository for AD and related dementia (ADRD).METHODSThe website makes available >70 genome-wide summary statistics datasets from GWAS and genome sequencing analysis for AD/ADRD. Variants identified from these datasets are mapped to up-to-date variant and gene annotations from a variety of resources and linked to functional genomics data.The database is powered by a big data optimized relational database and ontologies to consistently annotate study designs and phenotypes, facilitating data harmonization and efficient real-time data analysis and variant or gene report generation.RESULTSDetailed variant reports provide tabular and interactive graphical summaries of known ADRD associations, as well as highlight variants flagged by the Alzheimer’s Disease Sequencing Project (ADSP). Gene reports provide summaries of co-located ADRD risk-associated variants and have been expanded to include meta-analysis results from aggregate association tests performed by the ADSP allowing us to flag genes with genetic-evidence for AD.DISCUSSIONThe GenomicsDB makes available >100 million variant annotations, including ~30 million (5 million novel) variants identified as AD-relevant by ADSP, for browsing and real-time mining via the website or programmatically through a REST API. With a newly redesigned, efficient, search interface and comprehensive record pages linking summary statistics to variant and gene annotations, this resource makes these data both accessible and interpretable, establishing itself as valuable tool for AD research.

scholarly journals The Genetic Relationship between Interleukin Genes in Alzheimer’s Disease

2016 ◽  
Vol 6 (5) ◽  
Author(s):  
Myung Jin Mun ◽  
Sue Kyung Kim ◽  
Jin Ho Kim ◽  
Ji Young Choi ◽  
Won Cheoul Jang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Relationship

scholarly journals Pleiotropy of Alzheimer’s Disease and Educational Attainment: Insights from the Summary Statistics

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 986-986
Author(s):  
Yury Loika ◽  
Elena Loiko ◽  
Irina Culminskaya ◽  
Alexander Kulminski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Educational Attainment ◽  
Large Scale ◽  
Association Studies ◽  
Epidemiological Studies ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Nucleotide Polymorphisms ◽  
Omnibus Test

Abstract Epidemiological studies report beneficial associations of higher educational attainment (EDU) with Alzheimer’s disease (AD). Prior genome-wide association studies (GWAS) also reported variants associated with AD and EDU separately. The analysis of pleiotropic predisposition to these phenotypes may shed light on EDU-related protection against AD. We examined pleiotropic predisposition to AD and EDU using Fisher’s method and omnibus test applied to summary statistics for single nucleotide polymorphisms (SNPs) associated with AD and EDU in large-scale univariate GWAS at suggestive-effect (5×10-8

Herpesvirus Infections and Alzheimer’s Disease: A Mendelian Randomization Study 

2021 ◽  
Author(s):  
Shu-Yi Huang ◽  
Yu-Xiang Yang ◽  
Kevin Kuo ◽  
Hong-Qi Li ◽  
Xue-Ning Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Primary Analysis ◽  
Varicella Zoster ◽  
History Of

Abstract BackgroundObservational studies have suggested that herpesvirus infection increased the risk of Alzheimer’s disease (AD), but it is unclear whether the association is causal. The aim of the present study is to evaluate the causal relationship between four herpesvirus infections and AD. MethodsWe performed a two-sample Mendelian randomization analysis to investigate association of four active herpesvirus infections with AD using summary statistics from genome-wide association studies. The four herpesvirus infections (i.e., chickenpox, shingles, cold sores, mononucleosis) are caused by varicella-zoster virus, herpes simplex virus type 1, and Epstein-Barr virus (EBV), respectively. A large summary statistics data from International Genomics of Alzheimer’s Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was further performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD and 272,244 controls).ResultsWe found evidence of a suggestive association between mononucleosis (caused by EBV) and risk of AD (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.092-2.446, P = 0.017) after Bonferroni correction. It has been verified in validation analysis that mononucleosis is also associated with family history of AD (OR [95% CI] = 1.392 [1.061, 1.826], P=0.017). Genetically predicted shingles were associated with AD risk (OR [95% CI] = 0.867 [0.784, 0.958], P = 0.005). While genetically predicted chickenpox was suggestively associated with increased family history of AD (OR [95% CI] = 1.147 [1.007, 1.307], P = 0.039).ConclusionsOur findings provided evidence supporting a positive relationship between mononucleosis and AD, indicating a causal link between EBV infection and AD. Further elucidations of this association and underlying mechanisms are likely to identify feasible interventions to promote AD prevention.

scholarly journals Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease

2018 ◽  
Vol 137 (2) ◽  
pp. 209-226 ◽  
Author(s):  
Iris J. Broce ◽  
Chin Hong Tan ◽  
Chun Chieh Fan ◽  
Iris Jansen ◽  
Jeanne E. Savage ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Genetic Relationship

scholarly journals Estimating the causal effect of hearing loss on Alzheimer’s disease: a Mendelian randomisation study

2020 ◽  
Author(s):  
Benjamin M Jacobs ◽  
Alastair J Noyce ◽  
Christopher JD Hardy ◽  
Jason D Warren ◽  
Charles R Marshall
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Causal Effect ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Summary Statistics ◽  
Age Related ◽  
Hearing Difficulty

AbstractBackgroundHearing loss has been identified as one of the most important risk factors for Alzheimer’s disease (AD). However, the causality of this association has not been established.MethodsWe used publicly available GWAS summary statistics to construct instrumental variables for age-related hearing difficulty. We tested these genetic instruments for association with the outcome of AD using AD GWAS summary statistics in a two-sample Mendelian randomisation analysis. We used inverse-variance weighted meta-analysis to estimate the causal effect of hearing-related traits on AD, followed by secondary sensitivity analyses including a mixture of experts approach.ResultsThere was no strong evidence for a causal relationship between genetically-determined hearing difficulty (ORFE-IVW 1.27, 95% CI 0.89 to 1.82, p=0.189) and AD risk. There was no evidence to suggest that unbalanced horizontal pleiotropy was biasing the result. Power calculations indicated our instruments were sufficiently powered to detect the magnitude of effect described in case-control and cohort settings.ConclusionsOur results suggest that the size of the observed relationship between hearing loss and AD cannot be completely accounted for by a direct causal influence. Hearing loss may have more utility as a risk marker for AD than as a modifiable risk factor.

scholarly journals Integrative analysis of eQTL and GWAS summary statistics reveals novel genes related to Alzheimer's disease

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Pradeep Varathan ◽  
Priyanka Gorijala ◽  
Tanner Y. Jacobson ◽  
Kwangsik Nho ◽  
Shannon L. Risacher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Integrative Analysis ◽  
Summary Statistics ◽  
Novel Genes

scholarly journals Exploring the genetic relationship between hearing impairment and Alzheimer's disease

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Brittany L. Mitchell ◽  
Jackson G. Thorp ◽  
David M. Evans ◽  
Dale R. Nyholt ◽  
Nicholas G. Martin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Impairment ◽  
Genetic Relationship

scholarly journals A Bayesian approach to mediation analysis predicts 206 causal target genes in Alzheimer’s disease

2017 ◽  
Author(s):  
Yongjin Park ◽  
Abhishek K Sarkar ◽  
Liang He ◽  
Jose Davila-Velderrain ◽  
Philip L De Jager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Target Genes ◽  
Human Genetics ◽  
Fundamental Problem ◽  
Disease Genes ◽  
Summary Statistics ◽  
Intermediate Phenotypes ◽  
Causal Genes ◽  
Bayesian Inference Framework

AbstractCharacterizing the intermediate phenotypes, such as gene expression, that mediate genetic effects on complex diseases is a fundamental problem in human genetics. Existing methods utilize genotypic data and summary statistics to identify putative disease genes, but cannot distinguish pleiotropy from causal mediation and are limited by overly strong assumptions about the data. To overcome these limitations, we develop Causal Multivariate Mediation within Extended Linkage disequilibrium (CaMMEL), a novel Bayesian inference framework to jointly model multiple mediated and unmediated effects relying only on summary statistics. We show in simulation that CaMMEL accurately distinguishes between mediating and pleiotropic genes unlike existing methods. We applied CaMMEL to Alzheimer’s disease (AD) and found 206 causal genes in sub-threshold loci (p < 10−4). We prioritized 21 genes which mediate at least 5% of local genetic variance, disrupting innate immune pathways in AD.

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