- Analysis Name and Accession
Name: A Genome-Wide Association Meta-Analysis Of The Rate Of Change In Forced Expiratory Volume In The First Second (FEV1) In 14 Longitudinal Cohorts Of European Ancestry
- Analysis Description
- The Cohorts for Heart and Aging Research in Genomic Epimiology (CHARGE) consortium was formed to facilitate genome-wide association study meta-analyses and replication among large, well-phenotyped cohort studies. CHARGE has incorporated many genomic and phenotypic data from other cohorts, depending on the phenotype. The basic design was estimation of SNP effects on the continuous variable FEV1, taken at multiple time points within each of the 14 cohorts, with measurements in 27,249 adults of European ancestry. The GWAS meta-analysis was conducted in those with repeated measurements using a mixed effects model. Each cohort performed GWAS using a linear mixed effects model with a random intercept and random slope, with fixed effects for time, SNP, SNPxtime interaction, and baseline age, sex, standing height, smoking pattern during follow-up, smokingxtime interaction, baseline smoking pack-years, study site (as needed) and principal components of ancestry (as needed).
- Analysis Methods
- Each study independently implemented a predefined GWAS analysis plan. Each contributing cohort had its own GWAS platform, variant calling algorithm, call rate filter, HWE filter, MAF filter and analytic software (ProbABEL, SNPTEST, GenABEL, GWAF, PLINK, MACH2QTL, R-scripts). For the FEV1 trait, observed over time, the association with SNP genotypes used a 1 df additive model adjusted for covariates. Study-specific results for the SNPxtime interaction term (β), which estimates the effect of genotype on the rate of change in FEV1, were shared and meta-analyses using all 14 cohorts were conducted using METAL software with inverse variant weighting to combine effect estimates after applying genomic control correction.
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