A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population
Background: Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present...
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MDPI AG
2023-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/16/1/79 |
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| author | Shitao Rao Xiaotong Chen Olivia Yanlai Ou Sek Ying Chair Wai Tong Chien Guangming Liu Mary Miu Yee Waye |
| author_facet | Shitao Rao Xiaotong Chen Olivia Yanlai Ou Sek Ying Chair Wai Tong Chien Guangming Liu Mary Miu Yee Waye |
| author_sort | Shitao Rao |
| collection | DOAJ |
| description | Background: Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present study aimed to investigate causal correlation of the two diseases by a Mendelian randomization (MR) study and further elucidate the underlying molecular mechanisms. Methods: With the biggest summary datasets of a genome-wide association study (GWAS) in the East Asian population, we conducted a two-sample, bidirectional MR study to assess the causal correlation between shrimp allergy (SA) and MDD. Subsequently, we identified the pleiotropic genes’ susceptibility to the two diseases at whole-genome and tissue-specific levels, respectively. Enriched GO sets and KEGG pathways were also discovered to elucidate the potential underlying mechanisms. Results: With the most suitable MR method, SA was identified as a causal risk factor for MDD based on three different groups of independent genetic instruments, respectively (<i>p</i> < 2.81 × 10<sup>−2</sup>). In contrast, we did not observe a significant causal effect of MDD on SA. The GWAS-pairwise program successfully identified seven pleiotropic genetic variants (PPA3 > 0.8), indicating that the two diseases indeed have a shared genetic basis. At a whole-genome level, the MAGMA program identified 44 pleiotropic genes, which were enriched in allergy-related pathways, such as antigen processing and presentation pathway (<i>p</i> = 1.46 × 10<sup>−2</sup>). In brain-specific tissue, the S-MultiXcan program found 17 pleiotropic genes that were significantly enriched in immune-related pathways and GO sets, including asthma-related pathway, T-cell activation-related, and major histocompatibility complex protein-related GO sets. Regarding whole-blood tissue, the program identified six pleiotropic genes that are significantly enriched in tolerance induction-related GO sets. Conclusions: The present study for the first time indicated a significant causal effect of SA on the occurrence of MDD, but the reverse was not true. Enrichment analyses of pleiotropic genes at whole-genome and tissue-specific levels implied the involvement of allergy and immune-related pathways in the shared genetic mechanism of the two diseases. Elucidating the causal effect and the acting direction may be beneficial in reducing the incidence rate of MDD for the massive group of SA patients in the East Asian region. |
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| institution | Directory Open Access Journal |
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| spelling | doaj.art-0590521c914d4129b895e089a6813bad2024-01-10T15:05:27ZengMDPI AGNutrients2072-66432023-12-011617910.3390/nu16010079A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian PopulationShitao Rao0Xiaotong Chen1Olivia Yanlai Ou2Sek Ying Chair3Wai Tong Chien4Guangming Liu5Mary Miu Yee Waye6Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Psychology, University of Toronto, Toronto, ON M5S 1A1, CanadaCroucher Laboratory for Human Genomics, Asia-Pacific Genomic and Genetic Nursing Centre, The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong, ChinaCroucher Laboratory for Human Genomics, Asia-Pacific Genomic and Genetic Nursing Centre, The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong, ChinaCollege of Ocean Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen 361021, ChinaCroucher Laboratory for Human Genomics, Asia-Pacific Genomic and Genetic Nursing Centre, The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong, ChinaBackground: Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present study aimed to investigate causal correlation of the two diseases by a Mendelian randomization (MR) study and further elucidate the underlying molecular mechanisms. Methods: With the biggest summary datasets of a genome-wide association study (GWAS) in the East Asian population, we conducted a two-sample, bidirectional MR study to assess the causal correlation between shrimp allergy (SA) and MDD. Subsequently, we identified the pleiotropic genes’ susceptibility to the two diseases at whole-genome and tissue-specific levels, respectively. Enriched GO sets and KEGG pathways were also discovered to elucidate the potential underlying mechanisms. Results: With the most suitable MR method, SA was identified as a causal risk factor for MDD based on three different groups of independent genetic instruments, respectively (<i>p</i> < 2.81 × 10<sup>−2</sup>). In contrast, we did not observe a significant causal effect of MDD on SA. The GWAS-pairwise program successfully identified seven pleiotropic genetic variants (PPA3 > 0.8), indicating that the two diseases indeed have a shared genetic basis. At a whole-genome level, the MAGMA program identified 44 pleiotropic genes, which were enriched in allergy-related pathways, such as antigen processing and presentation pathway (<i>p</i> = 1.46 × 10<sup>−2</sup>). In brain-specific tissue, the S-MultiXcan program found 17 pleiotropic genes that were significantly enriched in immune-related pathways and GO sets, including asthma-related pathway, T-cell activation-related, and major histocompatibility complex protein-related GO sets. Regarding whole-blood tissue, the program identified six pleiotropic genes that are significantly enriched in tolerance induction-related GO sets. Conclusions: The present study for the first time indicated a significant causal effect of SA on the occurrence of MDD, but the reverse was not true. Enrichment analyses of pleiotropic genes at whole-genome and tissue-specific levels implied the involvement of allergy and immune-related pathways in the shared genetic mechanism of the two diseases. Elucidating the causal effect and the acting direction may be beneficial in reducing the incidence rate of MDD for the massive group of SA patients in the East Asian region.https://www.mdpi.com/2072-6643/16/1/79shrimp allergymajor depressive disorderEast AsianMendelian randomizationpleiotropic genesshared genetic basis |
| spellingShingle | Shitao Rao Xiaotong Chen Olivia Yanlai Ou Sek Ying Chair Wai Tong Chien Guangming Liu Mary Miu Yee Waye A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population Nutrients shrimp allergy major depressive disorder East Asian Mendelian randomization pleiotropic genes shared genetic basis |
| title | A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population |
| title_full | A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population |
| title_fullStr | A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population |
| title_full_unstemmed | A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population |
| title_short | A Positive Causal Effect of Shrimp Allergy on Major Depressive Disorder Mediated by Allergy- and Immune-Related Pathways in the East Asian Population |
| title_sort | positive causal effect of shrimp allergy on major depressive disorder mediated by allergy and immune related pathways in the east asian population |
| topic | shrimp allergy major depressive disorder East Asian Mendelian randomization pleiotropic genes shared genetic basis |
| url | https://www.mdpi.com/2072-6643/16/1/79 |
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