Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S]
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wid...
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Elsevier
2017-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520338335 |
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| author | Yao Hu Toshiko Tanaka Jingwen Zhu Weihua Guan Jason H.Y. Wu Bruce M. Psaty Barbara McKnight Irena B. King Qi Sun Melissa Richard Ani Manichaikul Alexis C. Frazier-Wood Edmond K. Kabagambe Paul N. Hopkins Jose M. Ordovas Luigi Ferrucci Stefania Bandinelli Donna K. Arnett Yii-Der I. Chen Shuang Liang David S. Siscovick Michael Y. Tsai Stephen S. Rich Myriam Fornage Frank B. Hu Eric B. Rimm Majken K. Jensen Rozenn N. Lemaitre Dariush Mozaffarian Lyn M. Steffen Andrew P. Morris Huaixing Li Xu Lin |
| author_facet | Yao Hu Toshiko Tanaka Jingwen Zhu Weihua Guan Jason H.Y. Wu Bruce M. Psaty Barbara McKnight Irena B. King Qi Sun Melissa Richard Ani Manichaikul Alexis C. Frazier-Wood Edmond K. Kabagambe Paul N. Hopkins Jose M. Ordovas Luigi Ferrucci Stefania Bandinelli Donna K. Arnett Yii-Der I. Chen Shuang Liang David S. Siscovick Michael Y. Tsai Stephen S. Rich Myriam Fornage Frank B. Hu Eric B. Rimm Majken K. Jensen Rozenn N. Lemaitre Dariush Mozaffarian Lyn M. Steffen Andrew P. Morris Huaixing Li Xu Lin |
| author_sort | Yao Hu |
| collection | DOAJ |
| description | MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology. |
| first_indexed | 2024-12-17T12:35:30Z |
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| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T12:35:30Z |
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| series | Journal of Lipid Research |
| spelling | doaj.art-44c9aaa4c707484ead48ec7020a3aff92022-12-21T21:48:18ZengElsevierJournal of Lipid Research0022-22752017-05-01585974981Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S]Yao Hu0Toshiko Tanaka1Jingwen Zhu2Weihua Guan3Jason H.Y. Wu4Bruce M. Psaty5Barbara McKnight6Irena B. King7Qi Sun8Melissa Richard9Ani Manichaikul10Alexis C. Frazier-Wood11Edmond K. Kabagambe12Paul N. Hopkins13Jose M. Ordovas14Luigi Ferrucci15Stefania Bandinelli16Donna K. Arnett17Yii-Der I. Chen18Shuang Liang19David S. Siscovick20Michael Y. Tsai21Stephen S. Rich22Myriam Fornage23Frank B. Hu24Eric B. Rimm25Majken K. Jensen26Rozenn N. Lemaitre27Dariush Mozaffarian28Lyn M. Steffen29Andrew P. Morris30Huaixing Li31Xu Lin32The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of ChinaTranslational Gerontology Branch, National Institute on Aging, Baltimore, MDThe Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of ChinaDivision of Biostatistics University of Minnesota, Minneapolis, MNGeorge Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, AustraliaCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA; Group Health Research Institute, Group Health Cooperative, Seattle, WADepartment of Biostatistics, University of Washington, Seattle, WADepartment of Internal Medicine, University of New Mexico, Albuquerque, NMChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MAInstitute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TXCenter for Public Health Genomics, University of Virginia, Charlottesville, VA; Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VAUSDA Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TXDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TNDepartment of Internal Medicine, University of Utah, Salt Lake City, UTNutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA; Department of Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, SpainTranslational Gerontology Branch, National Institute on Aging, Baltimore, MDGeriatric Unit, Azienda Sanitaria Firenze, Florence, ItalyDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, ALInstitute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CADepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MNCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA; New York Academy of Medicine, New York, NYDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MNCenter for Public Health Genomics, University of Virginia, Charlottesville, VAInstitute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TXChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MACardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WAFriedman School of Nutrition Science and Policy, Tufts University, Boston, MADivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MNGenetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, Oxford, United KingdomTo whom correspondence should be addressed. (X.L.); (H.L.); The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of ChinaTo whom correspondence should be addressed. (X.L.); (H.L.); The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of ChinaMUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.http://www.sciencedirect.com/science/article/pii/S0022227520338335geneticsfatty acid/desaturasesfatty acid/metabolismfatty acid/biosynthesismonounsaturated fatty acid |
| spellingShingle | Yao Hu Toshiko Tanaka Jingwen Zhu Weihua Guan Jason H.Y. Wu Bruce M. Psaty Barbara McKnight Irena B. King Qi Sun Melissa Richard Ani Manichaikul Alexis C. Frazier-Wood Edmond K. Kabagambe Paul N. Hopkins Jose M. Ordovas Luigi Ferrucci Stefania Bandinelli Donna K. Arnett Yii-Der I. Chen Shuang Liang David S. Siscovick Michael Y. Tsai Stephen S. Rich Myriam Fornage Frank B. Hu Eric B. Rimm Majken K. Jensen Rozenn N. Lemaitre Dariush Mozaffarian Lyn M. Steffen Andrew P. Morris Huaixing Li Xu Lin Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] Journal of Lipid Research genetics fatty acid/desaturases fatty acid/metabolism fatty acid/biosynthesis monounsaturated fatty acid |
| title | Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] |
| title_full | Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] |
| title_fullStr | Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] |
| title_full_unstemmed | Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] |
| title_short | Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations[S] |
| title_sort | discovery and fine mapping of loci associated with mufas through trans ethnic meta analysis in chinese and european populations s |
| topic | genetics fatty acid/desaturases fatty acid/metabolism fatty acid/biosynthesis monounsaturated fatty acid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520338335 |
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