Computational protocol: Meta-Analysis for Genome-Wide Association Study Identifies Multiple Variants at the BIN1 Locus Associated with Late-Onset Alzheimer's Disease

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Protocol publication

[…] Data cleaning and Quality control were performed with PLINK using the identical criteria for all Pfizer, ADNI and Genizon sample sets obtained from Illumina platforms. SNPs with MAF <1% or more than 1% missing values were removed, as were samples with more than 1% missing values. Hardy-Weinberg equilibrium (HWE) was evaluated in the control population. SNPs that were out of HWE (−log (p)>5) were dropped. Sample sets were checked for genetic outliers and duplicated samples, which were removed. Only one of any group of samples that are strongly related (IBS distance <0.1) was kept. Reported gender was cross-checked with genetic gender to identify any possible sample identification errors. SNPs with an excess of heterozygosity were removed (Het Excess>0.1 and HWE p<0.01). Caucasians were identified based on multi-dimensional scaling (MDS) of the data compare to the CEPH samples in the HapMap dataset. We adapted the QC procedure from the original GenADA set to accommodate the Affymetrix 550 k platform . We removed three additional subjects from the analysis set (subject ID 781, 6145 and 2803) who appear to be either admixture or more distant from the cluster formed by the other Caucasian subjects in the population stratification analysis. [...] The current GWAS analysis is based on association tests in individual markers without considering the joint effects of multiple variants. We employed GenGen to test whether the distribution of statistics from a group of genes in each pathway from BioCarta (http://www.biocarta.com/) is consistently deviated from the null hypothesis from our sample sets. Pfizer, ADNI and GenADA dataset (before imputation) were used for this analysis. 1000 permutations were conducted for each analysis. […]

Pipeline specifications

Software tools PLINK, ADMIXTURE, GenGen
Databases ADNI BioCarta
Applications Population genetic analysis, GWAS
Organisms Homo sapiens
Diseases Alzheimer Disease, Dementia