Differences in genetic risk score profiles for drug use disorder, major depression, and ADHD as a function of sex, age at onset, recurrence, mode of ascertainment, and treatment
(2023) In Psychological Medicine 53(8). p.3448-3460- Abstract
- Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment? Methods Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st-5th degree relatives in the Swedish population born 1932-1995 (n = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases. Results Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence,... (More)
- Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment? Methods Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st-5th degree relatives in the Swedish population born 1932-1995 (n = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases. Results Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence, ascertainment, and treatment with scores typically higher in cases with greater severity (e.g. early AAO, high recurrence, ascertainment in high intensity clinical settings, and treatment). However, severity was not always related to purer genetic profiles, as genetic risk for many disorders often increased together. However, some results, such as by mode of ascertainment from different Swedish registries, produced qualitative differences in FGRS profiles. Conclusions Differences in FGRS profiles for DUD, MD, and ADHD varied substantially by AAO, recurrence, ascertainment, and treatment. Replication of psychiatric studies, particularly those examining genetic factors, may be difficult unless cases are matched not only by diagnosis but by important clinical characteristics. Genetic correlations between psychiatric disorders could arise through one disorder impacting on the patterns of ascertainment for the other, rather than from the direct effects of shared genetic liabilities. (Less)
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https://lup.lub.lu.se/record/761dc44d-9492-4dfa-8ca1-83dbd500559e
- author
- Kendler, Kenneth S. LU ; Ohlsson, Henrik LU ; Bacanu, Silviu ; Sundquist, Jan LU and Sundquist, Kristina LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- age at onset, attention-deficit-hyperactivity disorder, drug use disorder, genetics, Major depression, recurrence
- in
- Psychological Medicine
- volume
- 53
- issue
- 8
- pages
- 3448 - 3460
- publisher
- Cambridge University Press
- external identifiers
-
- scopus:85124663873
- pmid:35098912
- ISSN
- 0033-2917
- DOI
- 10.1017/S0033291721005535
- language
- English
- LU publication?
- yes
- id
- 761dc44d-9492-4dfa-8ca1-83dbd500559e
- date added to LUP
- 2022-04-14 12:00:18
- date last changed
- 2024-04-12 03:00:07
@article{761dc44d-9492-4dfa-8ca1-83dbd500559e,
abstract = {{Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment? Methods Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st-5th degree relatives in the Swedish population born 1932-1995 (n = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases. Results Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence, ascertainment, and treatment with scores typically higher in cases with greater severity (e.g. early AAO, high recurrence, ascertainment in high intensity clinical settings, and treatment). However, severity was not always related to purer genetic profiles, as genetic risk for many disorders often increased together. However, some results, such as by mode of ascertainment from different Swedish registries, produced qualitative differences in FGRS profiles. Conclusions Differences in FGRS profiles for DUD, MD, and ADHD varied substantially by AAO, recurrence, ascertainment, and treatment. Replication of psychiatric studies, particularly those examining genetic factors, may be difficult unless cases are matched not only by diagnosis but by important clinical characteristics. Genetic correlations between psychiatric disorders could arise through one disorder impacting on the patterns of ascertainment for the other, rather than from the direct effects of shared genetic liabilities.}},
author = {{Kendler, Kenneth S. and Ohlsson, Henrik and Bacanu, Silviu and Sundquist, Jan and Sundquist, Kristina}},
issn = {{0033-2917}},
keywords = {{age at onset; attention-deficit-hyperactivity disorder; drug use disorder; genetics; Major depression; recurrence}},
language = {{eng}},
number = {{8}},
pages = {{3448--3460}},
publisher = {{Cambridge University Press}},
series = {{Psychological Medicine}},
title = {{Differences in genetic risk score profiles for drug use disorder, major depression, and ADHD as a function of sex, age at onset, recurrence, mode of ascertainment, and treatment}},
url = {{http://dx.doi.org/10.1017/S0033291721005535}},
doi = {{10.1017/S0033291721005535}},
volume = {{53}},
year = {{2023}},
}