Obesity-related RNA m⁶A demethylase gene FTO rs1421085 is associated with neuroticism in a longitudinal birth cohort...

Recent studies have suggested the involvement of brain RNA m⁶A methylation in stress response. One of the key players in the RNA m⁶A regulation is the demethylation catalysed by the fat mass and obesity-associated protein FTO, encoded by the fat mass and obesity-associated gene. Based on findings that experimental manipulation of the RNA m⁶A methylation in animal experiments can affect anxiety, and given that the C-allele of FTO rs1421085 had a significant association with indicators of overweight and obesity in our previous study, we have examined the possible association of FTO rs1421085 genotype with neuroticism in the same longitudinally observed sample. Data analysis included both birth cohorts of the Estonian Children Personality, Behaviour and Health Study (ECPBHS) that started in 1998/1999 when participants were 9 or 15 years old, respectively. Follow-ups were conducted at age 15, 18 and 25. Neuroticism at different ages was assessed with questionnaires of the five factor model. Statistically significant assocation between the FTO rs1421085 genotype and neuroticism emerged by age 25, with an additive effect of each T-allele. This association was largely based on females and was prominent in the older birth cohort at age 25, sampled during the Great Recession of 2007-2009. Conclusively, an overweight and obesity-related variant of FTO, the gene encoding an RNA m⁶A demethylase, was associated with lower neuroticism, this association being subject to gender and cohort effects.