Genetic effects on information processing speed are moderated by age--converging results from three samples.

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• Information processing is a key cognitive trait underpinning executive functions.
• The Trail Making Test (TMT) is a widely used measure of information processing, known for its heritability.
• Previous genetic studies on TMT performance have not adequately considered age as a moderating factor.

Purpose of the Study:

• To investigate genome-wide associations with age-independent and age-dependent TMT performance.
• To identify genetic variants that modulate the relationship between age and TMT performance.
• To evaluate age-dependent genetic findings in an independent cohort.

Main Methods:

• Genome-wide association studies (GWASs) were conducted on two population-representative samples (MARS and LMU).
• Age-dependent GWAS findings were analyzed and validated in a third sample (Sydney MAS).
• Meta-analysis was used to combine GWAS results and assess statistical significance.

Main Results:

• No significant age-independent TMT associations were found after correction for multiple testing.
• A genome-wide significant age-moderated effect was identified between DSG1 gene variants and TMT-A performance (visual processing speed).
• The minor allele of rs2199301 in DSG1 showed a beneficial effect in younger adults and a detrimental effect in older adults.

Conclusions:

• DSG1 variants exhibit age-dependent effects on information processing speed.
• These findings suggest complex interactions between DSG1 gene function, age, and cognitive performance.
• The observed effects may be linked to DSG1's roles in cell adhesion and apoptosis.