TY - JOUR
T1 - Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders
AU - Zhang, Lusi
AU - Lizano, Paulo
AU - Guo, Bin
AU - Xu, Yanxun
AU - Rubin, Leah H.
AU - Hill, S. Kristian
AU - Alliey-Rodriguez, Ney
AU - Lee, Adam M.
AU - Wu, Baolin
AU - Keedy, Sarah K.
AU - Tamminga, Carol A.
AU - Pearlson, Godfrey D.
AU - Clementz, Brett A.
AU - Keshavan, Matcheri S.
AU - Gershon, Elliot S.
AU - Sweeney, John A.
AU - Bishop, Jeffrey R.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7
Y1 - 2022/7
N2 - Cardiometabolic disorders have known inflammatory implications, and peripheral measures of inflammation and cardiometabolic disorders are common in persons with psychotic disorders. Inflammatory signatures are also related to neurobiological and behavioral changes in psychosis. Relationships between systemic inflammation and cardiometabolic genetic risk in persons with psychosis have not been examined. Thirteen peripheral inflammatory markers and genome-wide genotyping were assessed in 122 participants (n = 86 psychosis, n = 36 healthy controls) of European ancestry. Cluster analyses of inflammatory markers classified higher and lower inflammation subgroups. Single-trait genetic risk scores (GRS) were constructed for each participant using previously reported GWAS summary statistics for the following traits: schizophrenia, bipolar disorder, major depressive disorder, coronary artery disease, type-2 diabetes, low-density lipoprotein, high-density lipoprotein, triglycerides, and waist-to-hip ratio. Genetic correlations across traits were quantified. Principal component (PC) analysis of the cardiometabolic GRSs generated six PC loadings used in regression models to examine associations with inflammation markers. Functional module discovery explored biological mechanisms of the inflammation association of cardiometabolic GRS genes. A subgroup of 38% persons with psychotic disorders was characterized with higher inflammation status. These higher inflammation individuals had lower BACS scores (p = 0.038) compared to those with lower inflammation. The first PC of the cardiometabolic GRS matrix was related to higher inflammation status in persons with psychotic disorders (OR = 2.037, p = 0.001). Two of eight modules within the functional interaction network of cardiometabolic GRS genes were enriched for immune processes. Cardiometabolic genetic risk may predispose some individuals with psychosis to elevated inflammation which adversely impacts cognition associated with illness.
AB - Cardiometabolic disorders have known inflammatory implications, and peripheral measures of inflammation and cardiometabolic disorders are common in persons with psychotic disorders. Inflammatory signatures are also related to neurobiological and behavioral changes in psychosis. Relationships between systemic inflammation and cardiometabolic genetic risk in persons with psychosis have not been examined. Thirteen peripheral inflammatory markers and genome-wide genotyping were assessed in 122 participants (n = 86 psychosis, n = 36 healthy controls) of European ancestry. Cluster analyses of inflammatory markers classified higher and lower inflammation subgroups. Single-trait genetic risk scores (GRS) were constructed for each participant using previously reported GWAS summary statistics for the following traits: schizophrenia, bipolar disorder, major depressive disorder, coronary artery disease, type-2 diabetes, low-density lipoprotein, high-density lipoprotein, triglycerides, and waist-to-hip ratio. Genetic correlations across traits were quantified. Principal component (PC) analysis of the cardiometabolic GRSs generated six PC loadings used in regression models to examine associations with inflammation markers. Functional module discovery explored biological mechanisms of the inflammation association of cardiometabolic GRS genes. A subgroup of 38% persons with psychotic disorders was characterized with higher inflammation status. These higher inflammation individuals had lower BACS scores (p = 0.038) compared to those with lower inflammation. The first PC of the cardiometabolic GRS matrix was related to higher inflammation status in persons with psychotic disorders (OR = 2.037, p = 0.001). Two of eight modules within the functional interaction network of cardiometabolic GRS genes were enriched for immune processes. Cardiometabolic genetic risk may predispose some individuals with psychosis to elevated inflammation which adversely impacts cognition associated with illness.
KW - Cardiometabolic syndrome
KW - Genetic risk score
KW - Peripheral inflammation
KW - Psychotic disorders
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U2 - 10.1016/j.bbih.2022.100459
DO - 10.1016/j.bbih.2022.100459
M3 - Article
C2 - 35496776
AN - SCOPUS:85133331998
SN - 2666-3546
VL - 22
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100459
ER -