TY - JOUR
T1 - Genome-wide analyses of smoking behaviors in schizophrenia
T2 - Findings from the Psychiatric Genomics Consortium
AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium
AU - Peterson, Roseann E.
AU - Bigdeli, Tim B.
AU - Ripke, Stephan
AU - Bacanu, Silviu Alin
AU - Gejman, Pablo V.
AU - Levinson, Douglas F.
AU - Li, Qingqin S.
AU - Rujescu, Dan
AU - Rietschel, Marcella
AU - Weinberger, Daniel R.
AU - Straub, Richard E.
AU - Walters, James T.R.
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
AU - Mowry, Bryan J.
AU - Ophoff, Roel A.
AU - Andreassen, Ole A.
AU - Esko, Tõnu
AU - Petryshen, Tracey L.
AU - Kendler, Kenneth S.
AU - Fanous, Ayman H.
N1 - Publisher Copyright:
© 2021
PY - 2021/5
Y1 - 2021/5
N2 - While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (rg = 0.159; P = 5.05 × 10−10), cigarettes-smoked-per-day (rg = 0.094; P = 0.006), and age-of-onset of smoking (rg = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg = 0.624, P = 0.002) and cigarettes-smoked-per-day (rg = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10−5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10−8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.
AB - While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (rg = 0.159; P = 5.05 × 10−10), cigarettes-smoked-per-day (rg = 0.094; P = 0.006), and age-of-onset of smoking (rg = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg = 0.624, P = 0.002) and cigarettes-smoked-per-day (rg = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10−5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10−8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.
KW - Cigarettes per day
KW - GWAS
KW - Genetics
KW - Pleiotropy
KW - Schizophrenia
KW - Smoking initiation
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U2 - 10.1016/j.jpsychires.2021.02.027
DO - 10.1016/j.jpsychires.2021.02.027
M3 - Article
C2 - 33691233
AN - SCOPUS:85102145407
SN - 0022-3956
VL - 137
SP - 215
EP - 224
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -