Item-level analyses reveal genetic heterogeneity in neuroticism

Mats Nagel, Kyoko Watanabe, Sven Stringer, Danielle Posthuma () and Sophie Sluis ()
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Mats Nagel: Section Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Medical Centre
Kyoko Watanabe: VU University Amsterdam
Sven Stringer: VU University Amsterdam
Danielle Posthuma: Section Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Medical Centre
Sophie Sluis: Section Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Medical Centre

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Genome-wide association studies (GWAS) of psychological traits are generally conducted on (dichotomized) sums of items or symptoms (e.g., case-control status), and not on the individual items or symptoms themselves. We conduct large-scale GWAS on 12 neuroticism items and observe notable and replicable variation in genetic signal between items. Within samples, genetic correlations among the items range between 0.38 and 0.91 (mean rg = .63), indicating genetic heterogeneity in the full item set. Meta-analyzing the two samples, we identify 255 genome-wide significant independent genomic regions, of which 138 are item-specific. Genetic analyses and genetic correlations with 33 external traits support genetic differences between the items. Hierarchical clustering analysis identifies two genetically homogeneous item clusters denoted depressed affect and worry. We conclude that the items used to measure neuroticism are genetically heterogeneous, and that biological understanding can be gained by studying them in genetically more homogeneous clusters.

Date: 2018
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DOI: 10.1038/s41467-018-03242-8

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