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Mediational pathways between aggregate genetic liability and nonfatal suicide attempt : A Swedish population-based cohort

Lannoy, Séverine ; Ohlsson, Henrik LU ; Stephenson, Mallory ; Sundquist, Jan LU ; Sundquist, Kristina LU and Edwards, Alexis C. LU (2024) In American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Abstract

Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRSSA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRSSA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15–25 years (Nfemales = 850,278 and Nmales = 899,366), 26–35... (More)

Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRSSA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRSSA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15–25 years (Nfemales = 850,278 and Nmales = 899,366), 26–35 years (Nfemales = 800,189 and Nmales = 861,774), and 36–45 years (Nfemales = 498,285 and Nmales = 535,831). The association between FGRSSA and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15–25 years, HRtotal = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25–36 years, HRtotal = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25–36 years) in females (HRtotal = 1.46 [1.44; 1.49], mediation = 7%) and males (HRtotal = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRSSA was higher at ages of 15–25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Cox model, mediation, psychiatric disorders, suicide attempt
in
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
publisher
International Society of Psychiatric Genetics
external identifiers
  • pmid:38366742
  • scopus:85185688362
ISSN
1552-4841
DOI
10.1002/ajmg.b.32974
language
English
LU publication?
yes
id
6589f254-390f-4a65-b5d8-9cd03d4882f4
date added to LUP
2024-03-20 11:34:39
date last changed
2024-04-17 11:02:38
@article{6589f254-390f-4a65-b5d8-9cd03d4882f4,
  abstract     = {{<p>Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRS<sub>SA</sub>) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRS<sub>SA</sub> and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15–25 years (N<sub>females</sub> = 850,278 and N<sub>males</sub> = 899,366), 26–35 years (N<sub>females</sub> = 800,189 and N<sub>males</sub> = 861,774), and 36–45 years (N<sub>females</sub> = 498,285 and N<sub>males</sub> = 535,831). The association between FGRS<sub>SA</sub> and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15–25 years, HR<sub>total</sub> = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25–36 years, HR<sub>total</sub> = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25–36 years) in females (HR<sub>total</sub> = 1.46 [1.44; 1.49], mediation = 7%) and males (HR<sub>total</sub> = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRS<sub>SA</sub> was higher at ages of 15–25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.</p>}},
  author       = {{Lannoy, Séverine and Ohlsson, Henrik and Stephenson, Mallory and Sundquist, Jan and Sundquist, Kristina and Edwards, Alexis C.}},
  issn         = {{1552-4841}},
  keywords     = {{Cox model; mediation; psychiatric disorders; suicide attempt}},
  language     = {{eng}},
  publisher    = {{International Society of Psychiatric Genetics}},
  series       = {{American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics}},
  title        = {{Mediational pathways between aggregate genetic liability and nonfatal suicide attempt : A Swedish population-based cohort}},
  url          = {{http://dx.doi.org/10.1002/ajmg.b.32974}},
  doi          = {{10.1002/ajmg.b.32974}},
  year         = {{2024}},
}