Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis
Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechan...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/5/1195 |
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| author | Yan Gao Xiaowen Hu Dandan Wang Jie Jiang Minghui Li Ying Qing Xuhan Yang Juan Zhang Yue Zhang Chunling Wan |
| author_facet | Yan Gao Xiaowen Hu Dandan Wang Jie Jiang Minghui Li Ying Qing Xuhan Yang Juan Zhang Yue Zhang Chunling Wan |
| author_sort | Yan Gao |
| collection | DOAJ |
| description | Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (r<sub>AA</sub> = −0.577, <i>p</i> < 0.01; r<sub>ω-6 LCPUFA</sub> = −0.626, <i>p</i> < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (OR<sub>AA</sub> = 0.986, OR<sub>GLA</sub> = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia. |
| first_indexed | 2024-03-11T07:14:55Z |
| format | Article |
| id | doaj.art-c5b6639799524ce693a014504eb4d8a7 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T07:14:55Z |
| publishDate | 2023-02-01 |
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| series | Nutrients |
| spelling | doaj.art-c5b6639799524ce693a014504eb4d8a72023-11-17T08:20:56ZengMDPI AGNutrients2072-66432023-02-01155119510.3390/nu15051195Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization AnalysisYan Gao0Xiaowen Hu1Dandan Wang2Jie Jiang3Minghui Li4Ying Qing5Xuhan Yang6Juan Zhang7Yue Zhang8Chunling Wan9Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, ChinaPolyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (r<sub>AA</sub> = −0.577, <i>p</i> < 0.01; r<sub>ω-6 LCPUFA</sub> = −0.626, <i>p</i> < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (OR<sub>AA</sub> = 0.986, OR<sub>GLA</sub> = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia.https://www.mdpi.com/2072-6643/15/5/1195schizophreniaarachidonic acidlong-chain polyunsaturated fatty acidMendelian randomizationcross-national study |
| spellingShingle | Yan Gao Xiaowen Hu Dandan Wang Jie Jiang Minghui Li Ying Qing Xuhan Yang Juan Zhang Yue Zhang Chunling Wan Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis Nutrients schizophrenia arachidonic acid long-chain polyunsaturated fatty acid Mendelian randomization cross-national study |
| title | Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis |
| title_full | Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis |
| title_fullStr | Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis |
| title_full_unstemmed | Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis |
| title_short | Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis |
| title_sort | association between arachidonic acid and the risk of schizophrenia a cross national study and mendelian randomization analysis |
| topic | schizophrenia arachidonic acid long-chain polyunsaturated fatty acid Mendelian randomization cross-national study |
| url | https://www.mdpi.com/2072-6643/15/5/1195 |
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