A Further Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and...

Area of Science:

• Genetics
• Neuroscience
• Psychology

Background:

• Lam et al. (2017) published a large-scale cognitive genome-wide association study (GWAS) meta-analysis.
• A subsequent commentary raised concerns regarding the study's methodology and findings.
• Lam et al. (2018) responded to the commentary, providing quality control metrics.

Purpose of the Study:

• To empirically evaluate the phenotype derived by Lam et al. (2017).
• To determine the genetic similarity of the derived phenotype to education and cognitive ability.
• To assess whether identified genome-wide significant loci are associated with education or cognitive ability.

Main Methods:

• Multi-trait analysis of genome-wide association study (MTAG) analysis was utilized.
• Genetic correlation was calculated between the derived phenotype and measures of education and cognitive ability.
• Genome-wide significant loci were examined for associations with education and cognitive ability.

Main Results:

• The phenotype derived by Lam et al. (2017) exhibited a genetic correlation of one with three measures of education.
• The phenotype was found to be more genetically similar to education than to cognitive ability.
• Genome-wide significant loci identified in the study were associated with education, not cognitive ability.

Conclusions:

• The phenotype identified in Lam et al. (2017) is more strongly associated with education than cognitive ability.
• The findings challenge the specificity of the associations reported for cognitive ability.
• Re-evaluation of genetic loci associations is warranted.