Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. A Dual Systems Genetics Approach Identifies Common Genes, Networks, and Pathways for Type 1 and 2 Diabetes in Human Islets

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Mutation Load of Single, Large-Scale Deletions of mtDNA in Mitotic and Postmitotic Tissues

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Estimating Effect Sizes and Expected Replication Probabilities from GWAS Summary Statistics

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Bereavement among adult siblings: An examination of health service utilization and mental health outcomes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Associations between patterns in comorbid diagnostic trajectories of individuals with schizophrenia and etiological factors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Among patients with obsessive-compulsive disorder (OCD), 65-85% manifest another psychiatric disorder concomitantly or at some other time point during their life. OCD is highly heritable, as are many of its comorbidities. A possible genetic heterogeneity of OCD in relation to its comorbid conditions, however, has not yet been exhaustively explored. We used a framework of different approaches to study the genetic relationship of OCD with three commonly observed comorbidities, namely major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). First, using publicly available summary statistics from large-scale genome-wide association studies, we compared genetic correlation patterns for OCD, MDD, ADHD, and ASD with 861 somatic and mental health phenotypes. Secondly, we examined how polygenic risk scores (PRS) of eight traits that showed heterogeneous correlation patterns with OCD, MDD, ADHD, and ASD partitioned across comorbid subgroups in OCD using independent unpublished data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The comorbid subgroups comprised of patients with only OCD (N = 366), OCD and MDD (N = 1,052), OCD and ADHD (N = 443), OCD and ASD (N = 388), and OCD with more than 1 comorbidity (N = 429). We found that PRS of all traits but BMI were significantly associated with OCD across all subgroups (neuroticism: p = 1.19 × 10-32, bipolar disorder: p = 7.51 × 10-8, anorexia nervosa: p = 3.52 × 10-20, age at first birth: p = 9.38 × 10-5, educational attainment: p = 1.56 × 10-4, OCD: p = 1.87 × 10-6, insomnia: p = 2.61 × 10-5, BMI: p = 0.15). For age at first birth, educational attainment, and insomnia PRS estimates significantly differed across comorbid subgroups (p = 2.29 × 10-4, p = 1.63 × 10-4, and p = 0.045, respectively). Especially for anorexia nervosa, age at first birth, educational attainment, insomnia, and neuroticism the correlation patterns that emerged from genetic correlation analysis of OCD, MDD, ADHD, and ASD were mirrored in the PRS associations with the respective comorbid OCD groups. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across OCD comorbid subgroups.

OriginalsprogEngelsk
Artikelnummer711624
TidsskriftFrontiers in genetics
Vol/bind12
Sider (fra-til)711624
ISSN1664-8021
DOI
StatusUdgivet - 31 aug. 2021

Bibliografisk note

Copyright © 2021 Strom, Grove, Meier, Bækvad-Hansen, Becker Nissen, Damm Als, Halvorsen, Nordentoft, Mortensen, Hougaard, Werge, Mors, Børglum, Crowley, Bybjerg-Grauholm and Mattheisen.

ID: 67993250