Item-level analyses reveal genetic heterogeneity in neuroticism

Research output: Contribution to JournalArticleAcademicpeer-review

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 r g =.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.

Original languageEnglish
Article number905
Pages (from-to)1-10
Number of pages10
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2 Mar 2018

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Genetic Heterogeneity
Genome-Wide Association Study
Genes
genome
Cluster Analysis
Genome
Psychology
Neuroticism

Cite this

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title = "Item-level analyses reveal genetic heterogeneity in neuroticism",
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 r g =.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.",
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Item-level analyses reveal genetic heterogeneity in neuroticism. / Nagel, Mats; Watanabe, Kyoko; Stringer, Sven; Posthuma, Danielle; Van Der Sluis, Sophie.

In: Nature Communications, Vol. 9, No. 1, 905, 02.03.2018, p. 1-10.

Research output: Contribution to JournalArticleAcademicpeer-review

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