Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Selecting cases of major psychiatric and substance use disorders in Swedish national registries on the basis of clinical features to maximize the strength or specificity of the genetic risk

Kendler, Kenneth S. LU ; Ohlsson, Henrik LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2023) In Molecular Psychiatry
Abstract

We investigate how selection of psychiatric cases by phenotypic criteria can alter the strength and specificity of their genetic risk by examining samples from national Swedish registries for five disorders: major depression (MD, N = 158,557), drug use disorder (DUD, N = 69,841), bipolar disorder (BD, N = 13,530)) ADHD (N = 54,996) and schizophrenia (N = 11,227)). We maximized the family genetic risk score (FGRS) for each disorder and then the specificity of the FGRS in six disorder pairs by univariable and multivariable regression. We use split-half methods to divide our cases for each disorder into deciles for prediction of genetic risk magnitude and quintiles for prediction of specificity by FGRS differences between two disorders. We... (More)

We investigate how selection of psychiatric cases by phenotypic criteria can alter the strength and specificity of their genetic risk by examining samples from national Swedish registries for five disorders: major depression (MD, N = 158,557), drug use disorder (DUD, N = 69,841), bipolar disorder (BD, N = 13,530)) ADHD (N = 54,996) and schizophrenia (N = 11,227)). We maximized the family genetic risk score (FGRS) for each disorder and then the specificity of the FGRS in six disorder pairs by univariable and multivariable regression. We use split-half methods to divide our cases for each disorder into deciles for prediction of genetic risk magnitude and quintiles for prediction of specificity by FGRS differences between two disorders. We utilized seven predictor groups: demography/sex, # registrations, site of diagnosis, severity, comorbidity, treatment, and educational/social variables. The ratio of the FGRS in the upper vs two lower deciles from our multivariable prediction model was, in order, DUD – 12.6, MD – 4.9, BD – 4.5, ADHD – 3.3 and schizophrenia 1.4. From the lowest to highest quintile, our measures of genetic specificity increased more than five-fold for i) MD vs. Anxiety Disorders, ii) MD vs BD, iii) MD versus alcohol use disorder (AUD), iv) BD vs schizophrenia and v) DUD vs AUD. This increase was nearly two-fold for ADHD vs DUD. We conclude that the level of genetic liability for our psychiatric disorders could be substantially enriched by selection of cases with our predictors. Specificity of genetic risk could also be substantially impacted by these same predictors.

(Less)
Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Molecular Psychiatry
publisher
Nature Publishing Group
external identifiers
  • pmid:37414926
  • scopus:85164196862
ISSN
1359-4184
DOI
10.1038/s41380-023-02156-2
language
English
LU publication?
yes
id
ebc8bfac-e1bc-486f-ad87-303c9a0011e8
date added to LUP
2023-10-16 13:22:26
date last changed
2024-04-19 02:22:25
@article{ebc8bfac-e1bc-486f-ad87-303c9a0011e8,
  abstract     = {{<p>We investigate how selection of psychiatric cases by phenotypic criteria can alter the strength and specificity of their genetic risk by examining samples from national Swedish registries for five disorders: major depression (MD, N = 158,557), drug use disorder (DUD, N = 69,841), bipolar disorder (BD, N = 13,530)) ADHD (N = 54,996) and schizophrenia (N = 11,227)). We maximized the family genetic risk score (FGRS) for each disorder and then the specificity of the FGRS in six disorder pairs by univariable and multivariable regression. We use split-half methods to divide our cases for each disorder into deciles for prediction of genetic risk magnitude and quintiles for prediction of specificity by FGRS differences between two disorders. We utilized seven predictor groups: demography/sex, # registrations, site of diagnosis, severity, comorbidity, treatment, and educational/social variables. The ratio of the FGRS in the upper vs two lower deciles from our multivariable prediction model was, in order, DUD – 12.6, MD – 4.9, BD – 4.5, ADHD – 3.3 and schizophrenia 1.4. From the lowest to highest quintile, our measures of genetic specificity increased more than five-fold for i) MD vs. Anxiety Disorders, ii) MD vs BD, iii) MD versus alcohol use disorder (AUD), iv) BD vs schizophrenia and v) DUD vs AUD. This increase was nearly two-fold for ADHD vs DUD. We conclude that the level of genetic liability for our psychiatric disorders could be substantially enriched by selection of cases with our predictors. Specificity of genetic risk could also be substantially impacted by these same predictors.</p>}},
  author       = {{Kendler, Kenneth S. and Ohlsson, Henrik and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{1359-4184}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Molecular Psychiatry}},
  title        = {{Selecting cases of major psychiatric and substance use disorders in Swedish national registries on the basis of clinical features to maximize the strength or specificity of the genetic risk}},
  url          = {{http://dx.doi.org/10.1038/s41380-023-02156-2}},
  doi          = {{10.1038/s41380-023-02156-2}},
  year         = {{2023}},
}