Self-Reported Medication Use as an Alternate Phenotyping Method for Anxiety and Depression in the UK Biobank

TY - JOUR

T1 - Self-Reported Medication Use as an Alternate Phenotyping Method for Anxiety and Depression in the UK Biobank

AU - Skelton, Megan

AU - Rayner, Christopher

AU - Purves, Kirstin

AU - Coleman, Jonathan

AU - Gaspar, Héléna Alexandra

AU - Glanville, Kylie

AU - Hunjan, Avina

AU - Hübel, Christopher

AU - Breen, Gerome

AU - Eley, Thalia

N1 - Funding Information: This research was conducted using the UK Biobank Resource, under application number 18177. The authors would like to thank all individuals involved in UK Biobank, including the researchers, supporting organizations and of course all the participants who have made a vital contribution to improving health by sharing their experiences. T.C.E. and G.B. were part‐funded during this work by program grants from the UK Medical Research Council (MR/M021475/1 and MR/V012878/1). C.R. is supported by a grant from Fondation Peters to T.C.E. and G.B. G. B. has received honoraria, research or conference grants and consulting fees from Illumina and Otsuka. The authors acknowledge use of the research computing facility at King's College London, Rosalind ( https://rosalind.kcl.ac.uk ), which was part‐funded by capital equipment grants from Guy's and St Thomas' Charity (TR130505) and Maudsley Charity (Award 980). This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or King's College London. Publisher Copyright: © 2021 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.

PY - 2021/10/18

Y1 - 2021/10/18

N2 - The requirement for large sample sizes for psychiatric genetic analyses necessitates novel approaches to derive cases. Anxiety and depression show substantial genetic overlap and share pharmacological treatments. Data on prescribed medication could be effective for inferring case status when other indicators of mental health are unavailable. We investigated self-reported current medication use in UK Biobank participants of European ancestry. Medication Status cases reported using antidepressant or anxiolytic medication (n = 22,218), controls did not report psychotropic medication use (n = 168,959). A subset, “Medication Only,” additionally did not meet criteria for any other mental health indicator (case n = 2,643, control n = 107,029). We assessed genetic overlap between these phenotypes and two published genetic association studies of anxiety and depression, and an internalizing disorder trait derived from symptom-based questionnaires in UK Biobank. Genetic correlations between Medication Status and the three anxiety and depression phenotypes were significant (r g = 0.60–0.73). In the Medication Only subset, the genetic correlation with depression was significant (r g = 0.51). The three polygenic scores explained 0.33% – 0.80% of the variance in Medication Status and 0.07% – 0.19% of the variance in Medication Only. This study provides evidence that self-reported current medication use offers an alternate or supplementary anxiety or depression phenotype in genetic studies where diagnostic information is sparse or unavailable.

AB - The requirement for large sample sizes for psychiatric genetic analyses necessitates novel approaches to derive cases. Anxiety and depression show substantial genetic overlap and share pharmacological treatments. Data on prescribed medication could be effective for inferring case status when other indicators of mental health are unavailable. We investigated self-reported current medication use in UK Biobank participants of European ancestry. Medication Status cases reported using antidepressant or anxiolytic medication (n = 22,218), controls did not report psychotropic medication use (n = 168,959). A subset, “Medication Only,” additionally did not meet criteria for any other mental health indicator (case n = 2,643, control n = 107,029). We assessed genetic overlap between these phenotypes and two published genetic association studies of anxiety and depression, and an internalizing disorder trait derived from symptom-based questionnaires in UK Biobank. Genetic correlations between Medication Status and the three anxiety and depression phenotypes were significant (r g = 0.60–0.73). In the Medication Only subset, the genetic correlation with depression was significant (r g = 0.51). The three polygenic scores explained 0.33% – 0.80% of the variance in Medication Status and 0.07% – 0.19% of the variance in Medication Only. This study provides evidence that self-reported current medication use offers an alternate or supplementary anxiety or depression phenotype in genetic studies where diagnostic information is sparse or unavailable.

UR - http://www.scopus.com/inward/record.url?scp=85117085252&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32878

DO - 10.1002/ajmg.b.32878

M3 - Article

SN - 1552-4841

VL - 186

SP - 389

EP - 398

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 6

ER -