Author:
Nagel Mats,Jansen Philip R,Stringer Sven,Watanabe Kyoko,de Leeuw Christiaan A,Bryois Julien,Savage Jeanne E,Hammerschlag Anke R,Skene Nathan,Muñoz-Manchado Ana B,Linnarsson Sten,Hjerling-Leffler Jens,White Tonya JH,Tiemeier Henning,Polderman Tinca JC,Sullivan Patrick F,van der Sluis Sophie,Posthuma Danielle,
Abstract
Neuroticism is an important risk factor for psychiatric traits including depression1, anxiety2,3, and schizophrenia4–6. Previous genome-wide association studies7–12 (GWAS) reported 16 genomic loci10–12. Here we report the largest neuroticism GWAS meta-analysis to date (N=449,484), and identify 136 independent genome-wide significant loci (124 novel), implicating 599 genes. Extensive functional follow-up analyses show enrichment in several brain regions and involvement of specific cell-types, including dopaminergic neuroblasts (P=3×10-8), medium spiny neurons (P=4×10-8) and serotonergic neurons (P=1×10-7). Gene-set analyses implicate three specific pathways: neurogenesis (P=4.4×10-9), behavioural response to cocaine processes (P=1.84×10-7), and axon part (P=5.26×10-8). We show that neuroticism’s genetic signal partly originates in two genetically distinguishable subclusters13 (depressed affect and worry, the former being genetically strongly related to depression, rg=0.84), suggesting distinct causal mechanisms for subtypes of individuals. These results vastly enhance our neurobiological understanding of neuroticism, and provide specific leads for functional follow-up experiments.
Publisher
Cold Spring Harbor Laboratory
Reference43 articles.
1. The genetic and environmental relationship between major depression and the five-factor model of personality
2. Middeldorp C. M. et al. The Association of Personality with Anxious and Depressive Psychopathology. Biol. Personal. Individ. Differ. 251–272 (2006).
3. Association of Late Adolescent Personality With Risk for Subsequent Serious Mental Illness Among Men in a Swedish Nationwide Cohort Study;JAMA Psychiatry,2017
4. Limb proportions show developmental plasticity in response to embryo movement
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