ArticleScientific reports2026
Genome-wide association study of positive and negative affect reveals shared genetic architecture and a potential causal relationship with cognition.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Altered affect and cognitive dysfunction are burdensome features of many neuropsychiatric conditions that are highly comorbid, remain poorly understood, and have few efficacious treatments. Exploring their genetic architecture and causal relationships may provide insight into their aetiology and comorbidity. Compared to related but distinct traits (depression, wellbeing, neuroticism), findings from genome-wide association studies (GWAS) of positive and negative affect may be informative due to these phenotypes being less heterogenous (compared to broader phenotypes of wellbeing and depression), whilst still retaining important clinical relevance as potential targets for indirect intervention (compared to neuroticism which may be less modifiable). Using data from the Lifelines Cohort Study, we conducted the first GWAS of positive and negative affect using a validated measure (N = 57,946), and four cognitive domains: working memory, reaction time, learning and memory, and executive function (N ≥ 35,729). We then assessed genetic overlap and potential causal relationships using genetic correlation and bidirectional Mendelian randomization (MR) analyses, incorporating large GWAS on related-albeit distinct-phenotypes (depression, anxiety, wellbeing, general cognitive ability [GCA]). We identified one SNP that reached genome-wide significance (p < 5 × 10
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