Dataset Information

Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder.

ABSTRACT: UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire ("MHQ responders"). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB participants lacking MHQ data ("MHQ non-responders"; N_Training = 50%; N_Test = 50%), maximizing the informative sample for these traits. MHQ responders were more likely to be female, from higher socioeconomic positions, and less anxious than non-responders. Genetic correlation of GAD and PTSD between MHQ responders and non-responders ranged from 0.636 to 1.08; both were predicted by polygenic scores generated from independent cohorts. In meta-analyses of GAD (N = 489,579) and PTSD (N = 497,803), we discovered many novel genomic risk loci (13 for GAD and 40 for PTSD). Transcriptomic analyses converged on altered regulation of prenatal dorsolateral prefrontal cortex in these disorders. Our results provide one roadmap by which sample size and statistical power may be improved for gene discovery of incompletely ascertained traits in the UKB and other biobanks with limited mental health assessment.

SUBMITTER: Wendt FR

PROVIDER: S-EPMC9133008 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder.

Wendt Frank R FR Pathak Gita A GA Deak Joseph D JD De Angelis Flavio F Koller Dora D Cabrera-Mendoza Brenda B Lebovitch Dannielle S DS Levey Daniel F DF Stein Murray B MB Kranzler Henry R HR Koenen Karestan C KC Gelernter Joel J Huckins Laura M LM Polimanti Renato R

Molecular psychiatry 20220218 4

UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire ("MHQ responders"). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB participants lacking MHQ data ("MHQ non-responders"; N<sub>Training</sub> = 50%; N<sub>Test</sub> = 50%), maximizing the informative sample for these ...[more]

PMID: 35181757

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Project description:BackgroundLow- and middle-income countries bear a disproportionate burden of preterm birth (PTB) and low infant birth weight (LBW) complications where affective and anxiety disorders are more common in the antepartum period than in industrialized countries.ObjectiveTo evaluate the extent to which early pregnancy antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) are associated with infant birth weight and gestational age at delivery among a cohort of pregnant women in Peru.MethodsOur prospective cohort study consisted of 4408 pregnant women. Antepartum depression, generalized anxiety, and PTSD were assessed in early pregnancy using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist - Civilian Version, respectively. Pregnancy outcome data were obtained from medical records. Multivariable linear and logistic regression procedures were used to estimate adjusted measures of association (β coefficients and odds ratios) and 95% confidence intervals (CI).ResultsAfter adjusting for confounders, women with antepartum generalized anxiety (32.6% prevalence) had higher odds of LBW (adjusted odds ratio (OR)=1.47; 95%CI: 1.10-1.95) and were more likely to deliver small for gestational age (OR = 1.39; 95%CI: 1.01-1.92) infants compared to those without anxiety. Compared to those without PTSD, women with PTSD (34.5%) had higher odds of delivering preterm (OR = 1.28; 95%CI: 1.00-1.65) yet PTSD was not associated with LBW nor gestational age at delivery. Women with antepartum depression (26.2%) were at no increased risk of delivering a preterm, low-birth-weight or small-for-gestational-age infant.LimitationsOur ability to make casual inferences from this observational study is limited; however, these findings are consistent with prior studies.ConclusionGeneralized anxiety disorder during pregnancy appeared to increase odds of delivering a low-birth-weight or small-for-gestational-age infant, while PTSD was associated with increased odds of delivering preterm. Our findings, and those of others, suggest antenatal care should be tailored to screen for and provide additional mental health services to patients.

Dataset Information

Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder.

Publications

Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder.

Similar Datasets

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