TY - JOUR
T1 - Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition
T2 - a bidirectional and multivariable Mendelian randomization study with more than 815,000 participants
AU - Rosoff, Daniel B.
AU - Kaminsky, Zachary A.
AU - McIntosh, Andrew M.
AU - Davey Smith, George
AU - Lohoff, Falk W.
N1 - Funding Information:
This research was facilitated by the prior research of the Social Science Genetic Association Consortium (SSGAC), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the Psychiatric Genomics Consortium (PGC), and the Medical Research Council Integrative Epidemiology Unit (MRC-IEU, University of Bristol, UK), especially the developers of the MRC-IEU UK Biobank GWAS Pipeline. We gratefully acknowledge their contributing studies and the participants in those studies without whom this effort would not be possible. This work was supported by the National Institutes of Health (NIH) intramural funding [ZIA-AA000242 to F.W.L]; Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Wellcome Trust (Reference 104036/Z/14/Z to A.M.M.). George Davey Smith works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Rates of suicidal behavior are increasing in the United States and identifying causal risk factors continues to be a public health priority. Observational literature has shown that educational attainment (EA) and cognitive performance (CP) influence suicide attempt risk; however, the causal nature of these relationships is unknown. Using summary statistics from genome-wide association studies (GWAS) of EA, CP, and suicide attempt risk with > 815,000 combined white participants of European ancestry, we performed multivariable Mendelian randomization (MR) to disentangle the effects of EA and CP on attempted suicide. In single-variable MR (SVMR), EA and CP appeared to reduce suicide attempt risk (EA odds ratio (OR) per standard deviation (SD) increase in EA (4.2 years), 0.524, 95% CI, 0.412–0.666, P = 1.07 × 10−7; CP OR per SD increase in standardized score, 0.714, 95% CI, 0.577–0.885, P = 0.002). Conversely, bidirectional analyses found no effect of a suicide attempt on EA or CP. Using various multivariable MR (MVMR) models, EA seems to be the predominant risk factor for suicide attempt risk with the independent effect (OR, 0.342, 95% CI, 0.206–0.568, P = 1.61 × 10−4), while CP had no effect (OR, 1.182, 95% CI, 0.842–1.659, P = 0.333). In additional MVMR analyses accounting simultaneously for potential behavioral and psychiatric mediators (tobacco smoking; alcohol consumption; and self-reported nerves, tension, anxiety, or depression), the effect of EA was little changed (OR, 0.541, 95% CI, 0.421–0.696, P = 3.33 × 10−6). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our results show that even after accounting for psychiatric disorders and behavioral mediators, EA, but not CP, may causally influence suicide attempt risk among white individuals of European ancestry, which could have important implications for health policy and programs aimed at reducing the increasing rates of suicide. Future work is necessary to examine the EA–suicide relationship populations of different ethnicities.
AB - Rates of suicidal behavior are increasing in the United States and identifying causal risk factors continues to be a public health priority. Observational literature has shown that educational attainment (EA) and cognitive performance (CP) influence suicide attempt risk; however, the causal nature of these relationships is unknown. Using summary statistics from genome-wide association studies (GWAS) of EA, CP, and suicide attempt risk with > 815,000 combined white participants of European ancestry, we performed multivariable Mendelian randomization (MR) to disentangle the effects of EA and CP on attempted suicide. In single-variable MR (SVMR), EA and CP appeared to reduce suicide attempt risk (EA odds ratio (OR) per standard deviation (SD) increase in EA (4.2 years), 0.524, 95% CI, 0.412–0.666, P = 1.07 × 10−7; CP OR per SD increase in standardized score, 0.714, 95% CI, 0.577–0.885, P = 0.002). Conversely, bidirectional analyses found no effect of a suicide attempt on EA or CP. Using various multivariable MR (MVMR) models, EA seems to be the predominant risk factor for suicide attempt risk with the independent effect (OR, 0.342, 95% CI, 0.206–0.568, P = 1.61 × 10−4), while CP had no effect (OR, 1.182, 95% CI, 0.842–1.659, P = 0.333). In additional MVMR analyses accounting simultaneously for potential behavioral and psychiatric mediators (tobacco smoking; alcohol consumption; and self-reported nerves, tension, anxiety, or depression), the effect of EA was little changed (OR, 0.541, 95% CI, 0.421–0.696, P = 3.33 × 10−6). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our results show that even after accounting for psychiatric disorders and behavioral mediators, EA, but not CP, may causally influence suicide attempt risk among white individuals of European ancestry, which could have important implications for health policy and programs aimed at reducing the increasing rates of suicide. Future work is necessary to examine the EA–suicide relationship populations of different ethnicities.
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U2 - 10.1038/s41398-020-01047-2
DO - 10.1038/s41398-020-01047-2
M3 - Article
C2 - 33168806
AN - SCOPUS:85095720697
SN - 2158-3188
VL - 10
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 388
ER -