Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω<sub>3</sub>) fatty acids are polyunsaturated fatty acids (PUFAs) that are largely obtained from diet and have been speculated to decrease the inflammatory response that is...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14380 |
| _version_ | 1797465010770804736 |
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| author | Courtney Astore Sini Nagpal Greg Gibson |
| author_facet | Courtney Astore Sini Nagpal Greg Gibson |
| author_sort | Courtney Astore |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω<sub>3</sub>) fatty acids are polyunsaturated fatty acids (PUFAs) that are largely obtained from diet and have been speculated to decrease the inflammatory response that is involved in IBD; however, the causality of this association has not been established. A two-sample Mendelian randomization (MR) was used to assess genetic associations between 249 circulating metabolites measured in the UK Biobank as exposures and IBD as the outcome. The genome-wide association study summary level data for metabolite measurements and IBD were derived from large European ancestry cohorts. We observed ω<sub>3</sub> fatty acids as a significant protective association with IBD, with multiple modes of MR evidence replicated in three IBD summary genetic datasets. The instrumental variables that were involved in the causal association of ω<sub>3</sub> fatty acids with IBD highlighted an intronic SNP, rs174564, in <i>FADS2</i>, a protein engaged in the first step of alpha-linolenic acid desaturation leading to anti-inflammatory EPA and thence DHA production. A low ratio of ω<sub>3</sub> to ω<sub>6</sub> fatty acids was observed to be a causal risk factor, particularly for Crohn’s disease. ω<sub>3</sub> fatty acid supplementation may provide anti-inflammatory responses that are required to attenuate inflammation that is involved in IBD. |
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| format | Article |
| id | doaj.art-0f8e721bb07d4608823b5e121040b8ef |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:15:23Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0f8e721bb07d4608823b5e121040b8ef2023-11-24T08:43:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221438010.3390/ijms232214380Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel DiseaseCourtney Astore0Sini Nagpal1Greg Gibson2Center for Integrative Genomics, School of Biological Sciences, Georgia Institute of Technology, Krone EBB1 Building, 950 Atlantic Drive, Atlanta, GA 30332, USACenter for Integrative Genomics, School of Biological Sciences, Georgia Institute of Technology, Krone EBB1 Building, 950 Atlantic Drive, Atlanta, GA 30332, USACenter for Integrative Genomics, School of Biological Sciences, Georgia Institute of Technology, Krone EBB1 Building, 950 Atlantic Drive, Atlanta, GA 30332, USAInflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω<sub>3</sub>) fatty acids are polyunsaturated fatty acids (PUFAs) that are largely obtained from diet and have been speculated to decrease the inflammatory response that is involved in IBD; however, the causality of this association has not been established. A two-sample Mendelian randomization (MR) was used to assess genetic associations between 249 circulating metabolites measured in the UK Biobank as exposures and IBD as the outcome. The genome-wide association study summary level data for metabolite measurements and IBD were derived from large European ancestry cohorts. We observed ω<sub>3</sub> fatty acids as a significant protective association with IBD, with multiple modes of MR evidence replicated in three IBD summary genetic datasets. The instrumental variables that were involved in the causal association of ω<sub>3</sub> fatty acids with IBD highlighted an intronic SNP, rs174564, in <i>FADS2</i>, a protein engaged in the first step of alpha-linolenic acid desaturation leading to anti-inflammatory EPA and thence DHA production. A low ratio of ω<sub>3</sub> to ω<sub>6</sub> fatty acids was observed to be a causal risk factor, particularly for Crohn’s disease. ω<sub>3</sub> fatty acid supplementation may provide anti-inflammatory responses that are required to attenuate inflammation that is involved in IBD.https://www.mdpi.com/1422-0067/23/22/14380polygenic riskCrohn’s diseasedocasahexaenoic acidUK BioBank |
| spellingShingle | Courtney Astore Sini Nagpal Greg Gibson Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease International Journal of Molecular Sciences polygenic risk Crohn’s disease docasahexaenoic acid UK BioBank |
| title | Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease |
| title_full | Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease |
| title_fullStr | Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease |
| title_full_unstemmed | Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease |
| title_short | Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease |
| title_sort | mendelian randomization indicates a causal role for omega 3 fatty acids in inflammatory bowel disease |
| topic | polygenic risk Crohn’s disease docasahexaenoic acid UK BioBank |
| url | https://www.mdpi.com/1422-0067/23/22/14380 |
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