PT  - JOURNAL ARTICLE
AU  - Sandra M. Meier
AU  - Kalevi Trontti
AU  - Thomas Damm Als
AU  - Mikaela Laine
AU  - Marianne Giørtz Pedersen
AU  - Jonas Bybjerg-Grauholm
AU  - Marie Bækved-Hansen
AU  - Ewa Sokolowska
AU  - Preben B. Mortensen
AU  - David M. Hougaard
AU  - Thomas Werge
AU  - Merete Nordentoft
AU  - Anders D. Børglum
AU  - Iiris Hovatta
AU  - Manuel Mattheisen
AU  - Ole Mors
TI  - Genome-wide Association Study of Anxiety and Stress-related Disorders in the iPSYCH Cohort
AID  - 10.1101/263855
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 263855
4099  - http://biorxiv.org/content/early/2018/02/12/263855.short
4100  - http://biorxiv.org/content/early/2018/02/12/263855.full
AB  - Anxiety and stress-related disorders (ASRD) are among the most common mental disorders with the majority of patients suffering from additional disorders. Family and twin studies indicate that genetic and environmental factors are underlying their etiology. As ASRD are likely to configure various expressions of abnormalities in the basic stress-response system, we conducted a genome-wide association study including 12,655 cases with various anxiety and stress-related diagnoses and 19,225 controls. Standard association analyses were performed supplemented by a framework of sensitivity analyses. Variants in PDE4B showed consistent association with ASRD across a wide range of our analyses. In mice models, alternations in PDE4B expression were observed in those mice displaying anxious behavior after exposure to chronic stress. We also showed that 28% of the variance in ASRD was accounted for by common variants and that the genetic signature of ASRD overlapped with psychiatric traits, educational outcomes, obesity-related phenotypes, smoking, and reproductive success.