The Reelin (RELN) gene is associated with executive function in healthy individuals.

Executive functions such as set-shifting and maintenance are cognitive processes that rely on complex neurodevelopmental processes. Although neurodevelopmental processes are mainly studied in animal models and in neuropsychiatric disorders, the underlying genetic basis for these processes under physiological conditions is poorly understood. We aimed to investigate the association between genetic variants of the Reelin (RELN) gene and cognitive set-shifting in healthy young individuals. The relationship between 12 selected single nucleotide polymorphisms (SNPs) of the RELN gene and cognitive set-shifting as measured by perseverative errors using the modified card sorting test (MCST) was analysed in a sample of N=98 young healthy individuals (mean age in years: 22.7 ± 0.19). Results show that in individual MANCOVA analyses two of five significant SNPs (rs2711870: F(2,39)=7.14; p=0.0019; rs2249372: F(2,39)=6.97; p=0.002) withstood Bonferroni correction for multiple testing (corrected p-value: p=0.004). While haplotype analyses of the RELN gene showed significant associations between three haplotypes and perseverative error processing in various models of inheritance (adjusted for age, gender, BDI, MWTB IQ), the GCT haplotype showed the most robust finding with a recessive model of inheritance (p=2.32 × 10(-5)) involving the functional SNP rs362691 (Leu-Val amino acid change). Although our study strongly suggests the involvement of the RELN gene in cognitive set-shifting and maintenance, our study requires further exploration as well as replication of the findings in larger samples of healthy individuals and in clinical samples with neuropsychiatric disorders.