Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus
Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabo...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Ken Yoshida [verfasserIn] Kazuha Yokota [verfasserIn] Yukinobu Kutsuwada [verfasserIn] Kazuhiro Nakayama [verfasserIn] Kazuhisa Watanabe [verfasserIn] Ayumi Matsumoto [verfasserIn] Hiroshi Miyashita [verfasserIn] Seik‐soon Khor [verfasserIn] Katsushi Tokunaga [verfasserIn] Yosuke Kawai [verfasserIn] Masao Nagasaki [verfasserIn] Sadahiko Iwamoto [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Übergeordnetes Werk: |
In: Hepatology Communications - Wolters Kluwer Health/LWW, 2017, 4(2020), 8, Seite 1124-1135 |
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| Übergeordnetes Werk: |
volume:4 ; year:2020 ; number:8 ; pages:1124-1135 |
| Links: |
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| DOI / URN: |
10.1002/hep4.1529 |
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| Katalog-ID: |
DOAJ017104823 |
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| 245 | 1 | 0 | |a Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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| 520 | |a Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. | ||
| 653 | 0 | |a Diseases of the digestive system. Gastroenterology | |
| 700 | 0 | |a Kazuha Yokota |e verfasserin |4 aut | |
| 700 | 0 | |a Yukinobu Kutsuwada |e verfasserin |4 aut | |
| 700 | 0 | |a Kazuhiro Nakayama |e verfasserin |4 aut | |
| 700 | 0 | |a Kazuhisa Watanabe |e verfasserin |4 aut | |
| 700 | 0 | |a Ayumi Matsumoto |e verfasserin |4 aut | |
| 700 | 0 | |a Hiroshi Miyashita |e verfasserin |4 aut | |
| 700 | 0 | |a Seik‐soon Khor |e verfasserin |4 aut | |
| 700 | 0 | |a Katsushi Tokunaga |e verfasserin |4 aut | |
| 700 | 0 | |a Yosuke Kawai |e verfasserin |4 aut | |
| 700 | 0 | |a Masao Nagasaki |e verfasserin |4 aut | |
| 700 | 0 | |a Sadahiko Iwamoto |e verfasserin |4 aut | |
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10.1002/hep4.1529 doi (DE-627)DOAJ017104823 (DE-599)DOAJ989e2ed2ad6d4f4c886279dabe08baca DE-627 ger DE-627 rakwb eng RC799-869 Ken Yoshida verfasserin aut Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. Diseases of the digestive system. Gastroenterology Kazuha Yokota verfasserin aut Yukinobu Kutsuwada verfasserin aut Kazuhiro Nakayama verfasserin aut Kazuhisa Watanabe verfasserin aut Ayumi Matsumoto verfasserin aut Hiroshi Miyashita verfasserin aut Seik‐soon Khor verfasserin aut Katsushi Tokunaga verfasserin aut Yosuke Kawai verfasserin aut Masao Nagasaki verfasserin aut Sadahiko Iwamoto verfasserin aut In Hepatology Communications Wolters Kluwer Health/LWW, 2017 4(2020), 8, Seite 1124-1135 (DE-627)877444587 (DE-600)2881134-3 2471254X nnns volume:4 year:2020 number:8 pages:1124-1135 https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca kostenfrei https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/toc/2471-254X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2021 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2088 GBV_ILN_2118 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2020 8 1124-1135 |
| spelling |
10.1002/hep4.1529 doi (DE-627)DOAJ017104823 (DE-599)DOAJ989e2ed2ad6d4f4c886279dabe08baca DE-627 ger DE-627 rakwb eng RC799-869 Ken Yoshida verfasserin aut Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. Diseases of the digestive system. Gastroenterology Kazuha Yokota verfasserin aut Yukinobu Kutsuwada verfasserin aut Kazuhiro Nakayama verfasserin aut Kazuhisa Watanabe verfasserin aut Ayumi Matsumoto verfasserin aut Hiroshi Miyashita verfasserin aut Seik‐soon Khor verfasserin aut Katsushi Tokunaga verfasserin aut Yosuke Kawai verfasserin aut Masao Nagasaki verfasserin aut Sadahiko Iwamoto verfasserin aut In Hepatology Communications Wolters Kluwer Health/LWW, 2017 4(2020), 8, Seite 1124-1135 (DE-627)877444587 (DE-600)2881134-3 2471254X nnns volume:4 year:2020 number:8 pages:1124-1135 https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca kostenfrei https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/toc/2471-254X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2021 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2088 GBV_ILN_2118 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2020 8 1124-1135 |
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10.1002/hep4.1529 doi (DE-627)DOAJ017104823 (DE-599)DOAJ989e2ed2ad6d4f4c886279dabe08baca DE-627 ger DE-627 rakwb eng RC799-869 Ken Yoshida verfasserin aut Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. Diseases of the digestive system. Gastroenterology Kazuha Yokota verfasserin aut Yukinobu Kutsuwada verfasserin aut Kazuhiro Nakayama verfasserin aut Kazuhisa Watanabe verfasserin aut Ayumi Matsumoto verfasserin aut Hiroshi Miyashita verfasserin aut Seik‐soon Khor verfasserin aut Katsushi Tokunaga verfasserin aut Yosuke Kawai verfasserin aut Masao Nagasaki verfasserin aut Sadahiko Iwamoto verfasserin aut In Hepatology Communications Wolters Kluwer Health/LWW, 2017 4(2020), 8, Seite 1124-1135 (DE-627)877444587 (DE-600)2881134-3 2471254X nnns volume:4 year:2020 number:8 pages:1124-1135 https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca kostenfrei https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/toc/2471-254X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2021 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2088 GBV_ILN_2118 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2020 8 1124-1135 |
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10.1002/hep4.1529 doi (DE-627)DOAJ017104823 (DE-599)DOAJ989e2ed2ad6d4f4c886279dabe08baca DE-627 ger DE-627 rakwb eng RC799-869 Ken Yoshida verfasserin aut Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. Diseases of the digestive system. Gastroenterology Kazuha Yokota verfasserin aut Yukinobu Kutsuwada verfasserin aut Kazuhiro Nakayama verfasserin aut Kazuhisa Watanabe verfasserin aut Ayumi Matsumoto verfasserin aut Hiroshi Miyashita verfasserin aut Seik‐soon Khor verfasserin aut Katsushi Tokunaga verfasserin aut Yosuke Kawai verfasserin aut Masao Nagasaki verfasserin aut Sadahiko Iwamoto verfasserin aut In Hepatology Communications Wolters Kluwer Health/LWW, 2017 4(2020), 8, Seite 1124-1135 (DE-627)877444587 (DE-600)2881134-3 2471254X nnns volume:4 year:2020 number:8 pages:1124-1135 https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca kostenfrei https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/toc/2471-254X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2021 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2088 GBV_ILN_2118 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2020 8 1124-1135 |
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10.1002/hep4.1529 doi (DE-627)DOAJ017104823 (DE-599)DOAJ989e2ed2ad6d4f4c886279dabe08baca DE-627 ger DE-627 rakwb eng RC799-869 Ken Yoshida verfasserin aut Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. Diseases of the digestive system. Gastroenterology Kazuha Yokota verfasserin aut Yukinobu Kutsuwada verfasserin aut Kazuhiro Nakayama verfasserin aut Kazuhisa Watanabe verfasserin aut Ayumi Matsumoto verfasserin aut Hiroshi Miyashita verfasserin aut Seik‐soon Khor verfasserin aut Katsushi Tokunaga verfasserin aut Yosuke Kawai verfasserin aut Masao Nagasaki verfasserin aut Sadahiko Iwamoto verfasserin aut In Hepatology Communications Wolters Kluwer Health/LWW, 2017 4(2020), 8, Seite 1124-1135 (DE-627)877444587 (DE-600)2881134-3 2471254X nnns volume:4 year:2020 number:8 pages:1124-1135 https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca kostenfrei https://doi.org/10.1002/hep4.1529 kostenfrei https://doaj.org/toc/2471-254X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2021 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2088 GBV_ILN_2118 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2020 8 1124-1135 |
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Ken Yoshida @@aut@@ Kazuha Yokota @@aut@@ Yukinobu Kutsuwada @@aut@@ Kazuhiro Nakayama @@aut@@ Kazuhisa Watanabe @@aut@@ Ayumi Matsumoto @@aut@@ Hiroshi Miyashita @@aut@@ Seik‐soon Khor @@aut@@ Katsushi Tokunaga @@aut@@ Yosuke Kawai @@aut@@ Masao Nagasaki @@aut@@ Sadahiko Iwamoto @@aut@@ |
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We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the digestive system. 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R - Medicine |
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Ken Yoshida |
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Ken Yoshida misc RC799-869 misc Diseases of the digestive system. Gastroenterology Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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RC799-869 Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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misc RC799-869 misc Diseases of the digestive system. Gastroenterology |
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Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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Ken Yoshida Kazuha Yokota Yukinobu Kutsuwada Kazuhiro Nakayama Kazuhisa Watanabe Ayumi Matsumoto Hiroshi Miyashita Seik‐soon Khor Katsushi Tokunaga Yosuke Kawai Masao Nagasaki Sadahiko Iwamoto |
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genome‐wide association study of lean nonalcoholic fatty liver disease suggests human leukocyte antigen as a novel candidate locus |
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RC799-869 |
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Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
| abstract |
Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. |
| abstractGer |
Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. |
| abstract_unstemmed |
Nonalcoholic fatty liver disease (NAFLD) is supposed to manifest its metabolic phenotype in the liver, but it is common to have lean individuals diagnosed with NAFLD, known as lean NAFLD. We conducted a two‐stage analysis to identify NAFLD‐associated loci in Japanese patients. In stage I, 275 metabolically healthy normal‐weight patients with NAFLD were compared with 1,411 non‐NAFLD controls adjusted for age, sex, and alcohol consumption by a genome‐wide association study (GWAS). In stage II, human leukocyte antigen (HLA) in chromosome 6 (chr6) (P = 6.73E‐08), microRNA (MIR) MIR548F3 in chr7 (P = 4.25E‐07), myosin light chain 2 (MYL2) in chr12 (P = 4.39E‐07), and glycoprotein precursor (GPC)6 in chr13 (P = 5.43E‐07), as suggested by the GWAS, were assessed by single nucleotide polymorphism (SNP) association analysis of whole NAFLD against non‐NAFLD in 9,726 members of the general population. A minor allele of the secondary lead SNP in chr6, rs2076529, was significantly associated (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.11‐1.28; P = 2.10E‐06) and the lead SNP in chr7 was weakly associated (OR 1.15; 95% CI, 1.04‐1.27; P = 6.19E‐03) with increased NAFLD risk. Imputation‐based typing of HLA showed a significant difference in the distribution of HLA‐B, HLA‐DR‐beta chain 1 (DRB1), and HLA‐DQ‐beta chain 1 (DQB1) alleles in lean NAFLD GWAS. Next‐generation sequence‐based typing of HLA in 5,649 members of the general population replicated the significant difference of HLA‐B allele distribution and the significant increase of the HLA‐B*54:01 allele in whole NAFLD. Fecal metagenomic analysis of 3,420 members of the general population showed significant dissimilarity in beta‐diversity analysis of rs2076529 and HLA‐B*54:01 allele carriers from noncarriers. Veillonellaceae was increased but Verrucomicrobia was decreased in rs2076529 minor allele and HLA‐B*54:01 allele carriers as in NAFLD. Conclusion: HLA was identified as a novel locus associated with NAFLD susceptibility, which might be affected by the alteration of gut microbiota. |
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Genome‐Wide Association Study of Lean Nonalcoholic Fatty Liver Disease Suggests Human Leukocyte Antigen as a Novel Candidate Locus |
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https://doi.org/10.1002/hep4.1529 https://doaj.org/article/989e2ed2ad6d4f4c886279dabe08baca https://doaj.org/toc/2471-254X |
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Kazuha Yokota Yukinobu Kutsuwada Kazuhiro Nakayama Kazuhisa Watanabe Ayumi Matsumoto Hiroshi Miyashita Seik‐soon Khor Katsushi Tokunaga Yosuke Kawai Masao Nagasaki Sadahiko Iwamoto |
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Kazuha Yokota Yukinobu Kutsuwada Kazuhiro Nakayama Kazuhisa Watanabe Ayumi Matsumoto Hiroshi Miyashita Seik‐soon Khor Katsushi Tokunaga Yosuke Kawai Masao Nagasaki Sadahiko Iwamoto |
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10.1002/hep4.1529 |
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2024-07-04T00:20:11.053Z |
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