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Genetic associations in Alzheimer’s disease: A systematic review and meta‐analysis
Author(s) -
Hema Sree G.N.S,
Marisse Lakshmi Prasanna,
K Mamatha,
Vithal Abhigjyna,
Satish Kshreeraja S.,
Rajalekshmi Saraswathy Ganesan,
K. Radhika,
Burri Raghunath R.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037027
Subject(s) - meta analysis , publication bias , funnel plot , medline , systematic review , cochrane library , medicine , disease , bioinformatics , biology , pathology , biochemistry
Abstract Background Elucidation of genetic associations underlying Alzheimer’s Disease (AD) pathogenesis and progression is of prime importance in early diagnosis and drug discovery. Despite existence of innumerable studies to comprehend the genetic hallmarks of AD, inconsistencies amongst the studies in ascertaining specific genes involved in AD risk prompted this Systematic Review and Meta‐analysis. Method The review protocol was registered in Prospero (CRD42019127482). AD related Boolean search strategy was generated to retrieve case‐control studies evaluating genetic associations in AD patients from Pubmed/MEDLINE, Cochrane library, Proquest, Europe PMC, Grey literature, HuGE navigator, Latin American and Carribean Health Sciences literature published till March‐2019. Case‐control studies that defined AD diagnosis through standard diagnostic criteria were included. Preclinical and in‐silico studies were excluded. The shortlisted studies were critically appraised through New Castle Ottawa Scale (NOS) and Q‐Genie tool and the resultant data was extracted. Meta‐analysis was performed for Single Nucleotide Polymorphisms (SNPs) that were reported to be replicated in two different ethnicities by at‐least two studies through random effects model using Revman 5.3. Publication bias was assessed using Egger’s test, funnel plot, Begg and Mazumdar rank correlation test. Later, Interim Venice assessment and sensitivity analysis were executed to evaluate the credibility and versatility of the selected studies respectively. Result Among 352 285 studies retrieved, only 793 studies that met the eligibility criteria were critically appraised. This ultimately resulted in 118 studies for systematic review out of which, 23 SNPs corresponding to 15 genes were prioritized for meta‐analysis. The following SNPs were found to be significantly associated with AD risk: rs3865444 (CD33) (p = 0.04; I 2 = 40%; OR [CI] = 0.88 [0.78‐0.99]), rs7561528 (BIN1) (p = 0.03; I 2 = 46%; OR [CI] = 0.86 [0.76‐0.98]) and rs1801133 (MTHFR) (p = 0.007; I 2 = 18%; OR [CI] = 0.73 [0.61‐0.88]). Interim Venice criteria revealed moderate credibility for seven SNPs and weak credibility for 16 SNPs. Further, sensitivity analysis confirmed the versatility of the selected studies. Conclusion Our findings acknowledged significant associations of three SNPs: rs3865444, rs7561528 and rs1801133 with Alzheimer’s risk. This evidence has to be replicated further to substantiate the role of aforesaid SNPs in AD.