Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis
Coffee or caffeine consumption has been associated with neuropsychiatric disorders, implying a shared etiology. However, whether these associations reflect causality remains largely unknown. To understand the genetic structure of the association between decaffeinated coffee consumption (DCC) and neu...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.910432/full |
| _version_ | 1818518975284248576 |
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| author | Bian Yin Xinpei Wang Tao Huang Tao Huang Tao Huang Jinzhu Jia Jinzhu Jia |
| author_facet | Bian Yin Xinpei Wang Tao Huang Tao Huang Tao Huang Jinzhu Jia Jinzhu Jia |
| author_sort | Bian Yin |
| collection | DOAJ |
| description | Coffee or caffeine consumption has been associated with neuropsychiatric disorders, implying a shared etiology. However, whether these associations reflect causality remains largely unknown. To understand the genetic structure of the association between decaffeinated coffee consumption (DCC) and neuropsychiatric traits, we examined the genetic correlation, causality, and shared genetic structure between DCC and neuropsychiatric traits using linkage disequilibrium score regression, bidirectional Mendelian randomization (MR), and genome-wide cross-trait meta-analysis in large GWAS Consortia for coffee consumption (N = 329,671) and 13 neuropsychiatric traits (sample size ranges from 36,052 to 500,199). We found strong positive genetic correlations between DCC and lifetime cannabis use (LCU; Rg = 0.48, P = 8.40 × 10−19), alcohol use disorder identification test (AUDIT) total score (AUDIT_T; Rg = 0.40, P = 4.63 × 10−13), AUDIT_C score (alcohol consumption component of the AUDIT; Rg = 0.40, P = 5.26 × 10−11), AUDIT_P score (dependence and hazardous-use component of the AUDIT; Rg = 0.28, P = 1.36 × 10−05), and strong negative genetic correlations between DCC and neuroticism (Rg = −0.15, P = 7.27 × 10−05), major depressed diseases (MDD; Rg = −0.15, P = 0.0010), and insomnia (Rg= −0.15, P = 0.0007). In the cross-trait meta-analysis, we identified 6, 5, 1, 1, 2, 31, and 27 shared loci between DCC and Insomnia, LCU, AUDIT_T, AUDIT_C, AUDIT_P, neuroticism, and MDD, respectively, which were mainly enriched in bone marrow, lymph node, cervix, uterine, lung, and thyroid gland tissues, T cell receptor signaling pathway, antigen receptor-mediated signaling pathway, and epigenetic pathways. A large of TWAS-significant associations were identified in tissues that are part of the nervous system, digestive system, and exo-/endocrine system. Our findings further indicated a causal influence of liability to DCC on LCU and low risk of MDD (odds ratio: 0.90, P = 9.06 × 10−5 and 1.27, P = 7.63 × 10−4 respectively). We also observed that AUDIT_T and AUDIT_C were causally related to DCC (odds ratio: 1.83 per 1-SD increase in AUDIT_T, P = 1.67 × 10−05, 1.80 per 1-SD increase in AUDIT_C, P = 5.09 × 10−04). Meanwhile, insomnia and MDD had a causal negative influence on DCC (OR: 0.91, 95% CI: 0.86–0.95, P = 1.51 × 10−04 for Insomnia; OR: 0.93, 95% CI: 0.89–0.99, P = 6.02 × 10−04 for MDD). These findings provided evidence for the shared genetic basis and causality between DCC and neuropsychiatric diseases, and advance our understanding of the shared genetic mechanisms underlying their associations, as well as assisting with making recommendations for clinical works or health education. |
| first_indexed | 2024-12-11T01:17:34Z |
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| language | English |
| last_indexed | 2024-12-11T01:17:34Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-48d1c91ea280482cae627d09c48cca682022-12-22T01:25:50ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402022-07-011310.3389/fpsyt.2022.910432910432Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization AnalysisBian Yin0Xinpei Wang1Tao Huang2Tao Huang3Tao Huang4Jinzhu Jia5Jinzhu Jia6Department of Biostatistics, School of Public Health, Peking University, Beijing, ChinaDepartment of Biostatistics, School of Public Health, Peking University, Beijing, ChinaDepartment of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, ChinaCenter for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, Beijing, ChinaKey Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, ChinaDepartment of Biostatistics, School of Public Health, Peking University, Beijing, ChinaCenter for Statistical Science, Peking University, Beijing, ChinaCoffee or caffeine consumption has been associated with neuropsychiatric disorders, implying a shared etiology. However, whether these associations reflect causality remains largely unknown. To understand the genetic structure of the association between decaffeinated coffee consumption (DCC) and neuropsychiatric traits, we examined the genetic correlation, causality, and shared genetic structure between DCC and neuropsychiatric traits using linkage disequilibrium score regression, bidirectional Mendelian randomization (MR), and genome-wide cross-trait meta-analysis in large GWAS Consortia for coffee consumption (N = 329,671) and 13 neuropsychiatric traits (sample size ranges from 36,052 to 500,199). We found strong positive genetic correlations between DCC and lifetime cannabis use (LCU; Rg = 0.48, P = 8.40 × 10−19), alcohol use disorder identification test (AUDIT) total score (AUDIT_T; Rg = 0.40, P = 4.63 × 10−13), AUDIT_C score (alcohol consumption component of the AUDIT; Rg = 0.40, P = 5.26 × 10−11), AUDIT_P score (dependence and hazardous-use component of the AUDIT; Rg = 0.28, P = 1.36 × 10−05), and strong negative genetic correlations between DCC and neuroticism (Rg = −0.15, P = 7.27 × 10−05), major depressed diseases (MDD; Rg = −0.15, P = 0.0010), and insomnia (Rg= −0.15, P = 0.0007). In the cross-trait meta-analysis, we identified 6, 5, 1, 1, 2, 31, and 27 shared loci between DCC and Insomnia, LCU, AUDIT_T, AUDIT_C, AUDIT_P, neuroticism, and MDD, respectively, which were mainly enriched in bone marrow, lymph node, cervix, uterine, lung, and thyroid gland tissues, T cell receptor signaling pathway, antigen receptor-mediated signaling pathway, and epigenetic pathways. A large of TWAS-significant associations were identified in tissues that are part of the nervous system, digestive system, and exo-/endocrine system. Our findings further indicated a causal influence of liability to DCC on LCU and low risk of MDD (odds ratio: 0.90, P = 9.06 × 10−5 and 1.27, P = 7.63 × 10−4 respectively). We also observed that AUDIT_T and AUDIT_C were causally related to DCC (odds ratio: 1.83 per 1-SD increase in AUDIT_T, P = 1.67 × 10−05, 1.80 per 1-SD increase in AUDIT_C, P = 5.09 × 10−04). Meanwhile, insomnia and MDD had a causal negative influence on DCC (OR: 0.91, 95% CI: 0.86–0.95, P = 1.51 × 10−04 for Insomnia; OR: 0.93, 95% CI: 0.89–0.99, P = 6.02 × 10−04 for MDD). These findings provided evidence for the shared genetic basis and causality between DCC and neuropsychiatric diseases, and advance our understanding of the shared genetic mechanisms underlying their associations, as well as assisting with making recommendations for clinical works or health education.https://www.frontiersin.org/articles/10.3389/fpsyt.2022.910432/fullcoffee consumptionneuropsychiatric diseasesshared geneticsgenetic correlationMendelian randomizationcausality |
| spellingShingle | Bian Yin Xinpei Wang Tao Huang Tao Huang Tao Huang Jinzhu Jia Jinzhu Jia Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis Frontiers in Psychiatry coffee consumption neuropsychiatric diseases shared genetics genetic correlation Mendelian randomization causality |
| title | Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis |
| title_full | Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis |
| title_fullStr | Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis |
| title_full_unstemmed | Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis |
| title_short | Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis |
| title_sort | shared genetics and causality between decaffeinated coffee consumption and neuropsychiatric diseases a large scale genome wide cross trait analysis and mendelian randomization analysis |
| topic | coffee consumption neuropsychiatric diseases shared genetics genetic correlation Mendelian randomization causality |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.910432/full |
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