Infection Polygenic Factors Account for a Small Proportion of the Relationship Between Infections and Mental Disorders
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Infection Polygenic Factors Account for a Small Proportion of the Relationship Between Infections and Mental Disorders. / Shorter, John R.; Meijsen, Joeri; Nudel, Ron; Krebs, Morten; Gådin, Jesper; Mikkelsen, Dorte H.; Nogueira Avelar e Silva, Raquel; Benros, Michael E.; Thompson, Wesley K.; Ingason, Andrés; Werge, Thomas.
I: Biological Psychiatry, Bind 92, Nr. 4, 2022, s. 283-290.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Infection Polygenic Factors Account for a Small Proportion of the Relationship Between Infections and Mental Disorders
AU - Shorter, John R.
AU - Meijsen, Joeri
AU - Nudel, Ron
AU - Krebs, Morten
AU - Gådin, Jesper
AU - Mikkelsen, Dorte H.
AU - Nogueira Avelar e Silva, Raquel
AU - Benros, Michael E.
AU - Thompson, Wesley K.
AU - Ingason, Andrés
AU - Werge, Thomas
N1 - Publisher Copyright: © 2022 Society of Biological Psychiatry
PY - 2022
Y1 - 2022
N2 - Background: Several recent studies have suggested a role for infections in the development of mental disorders; however, the genetic contribution to this association is understudied. Methods: We use the iPSYCH case-cohort genotyped sample (n = 65,534) and Danish health care registry data to study the genetic association between infections and mental disorders. To test the hypothesis that these associations are due to genetic pleiotropy, we estimated the genetic correlation between infection and mental disorders. Polygenic risk scores (PRSs) were used to assess whether genetic pleiotropy of infections and mental disorders was mediated by actual infection diagnoses. Results: We observed that schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, and posttraumatic stress disorder (rg ranging between 0.18 and 0.83), but not autism spectrum disorder and anorexia nervosa, were significantly genetically correlated with infection diagnoses. PRSs for infections were associated with modest increase in risk of attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia in the iPSYCH case-cohort (hazard ratios = 1.04 to 1.10) but was not associated with risk of anorexia, autism, or bipolar disorder. Using mediation analysis, we show that infection diagnoses account for only a small proportion (6%–14%) of the risk for mental disorders conferred by infection PRSs. Conclusions: Infections and mental disorders share a modest genetic architecture. Infection PRSs can predict risk of certain mental disorders; however, this effect is moderate. Finally, recorded infections partially explain the relationship between infection PRSs and mental disorders.
AB - Background: Several recent studies have suggested a role for infections in the development of mental disorders; however, the genetic contribution to this association is understudied. Methods: We use the iPSYCH case-cohort genotyped sample (n = 65,534) and Danish health care registry data to study the genetic association between infections and mental disorders. To test the hypothesis that these associations are due to genetic pleiotropy, we estimated the genetic correlation between infection and mental disorders. Polygenic risk scores (PRSs) were used to assess whether genetic pleiotropy of infections and mental disorders was mediated by actual infection diagnoses. Results: We observed that schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, and posttraumatic stress disorder (rg ranging between 0.18 and 0.83), but not autism spectrum disorder and anorexia nervosa, were significantly genetically correlated with infection diagnoses. PRSs for infections were associated with modest increase in risk of attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia in the iPSYCH case-cohort (hazard ratios = 1.04 to 1.10) but was not associated with risk of anorexia, autism, or bipolar disorder. Using mediation analysis, we show that infection diagnoses account for only a small proportion (6%–14%) of the risk for mental disorders conferred by infection PRSs. Conclusions: Infections and mental disorders share a modest genetic architecture. Infection PRSs can predict risk of certain mental disorders; however, this effect is moderate. Finally, recorded infections partially explain the relationship between infection PRSs and mental disorders.
KW - Concordance index
KW - Genetic correlation
KW - iPSYCH
KW - Mediation analysis
KW - Pleiotropy
KW - Polygenic risk score
U2 - 10.1016/j.biopsych.2022.01.007
DO - 10.1016/j.biopsych.2022.01.007
M3 - Journal article
C2 - 35305821
AN - SCOPUS:85126521554
VL - 92
SP - 283
EP - 290
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 4
ER -
ID: 305715749