Large-scale association analyses identify host factors influencing human gut microbiome composition
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected...
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| Vydané v: | Nature genetics Ročník 53; číslo 2; s. 156 - 165 |
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| Médium: | Journal Article |
| Jazyk: | English |
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New York
Nature Publishing Group US
01.02.2021
Nature Publishing Group |
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| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
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| Abstract | To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (
P
< 5 × 10
−8
) threshold. One locus, the lactase (
LCT
) gene locus, reached study-wide significance (genome-wide association study signal:
P
= 1.28 × 10
−20
), and it showed an age-dependent association with
Bifidobacterium
abundance. Other associations were suggestive (1.95 × 10
−10
<
P
< 5 × 10
−8
) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations. |
|---|---|
| AbstractList | To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant ( P < 5 × 10 −8 ) threshold. One locus, the lactase ( LCT ) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10 −20 ), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 −10 < P < 5 × 10 −8 ) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10.sup.-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10.sup.-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10.sup.-10 < P < 5 × 10.sup.-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10.sup.-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10.sup.-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10.sup.-10 < P < 5 × 10.sup.-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant ( P < 5 × 10 −8 ) threshold. One locus, the lactase ( LCT ) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10 −20 ), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 −10 < P < 5 × 10 −8 ) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P &lt; 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) &lt; P &lt; 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 out of 410 genera were detected in more than 95% samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 31 loci affecting microbiome at a genome-wide significant (P<5×10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (GWAS signal P=1.28×10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95×10−10<P<5×10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome has causal effects in ulcerative colitis and rheumatoid arthritis. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10 ) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10 ), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 < P < 5 × 10 ) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10 < P < 5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10 < P < 5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. |
| Audience | Academic |
| Author | Moon, Jee-Young Kaplan, Robert C. Agreus, Lars Knight, Rob Weiss, Stefan Demirkan, Ayse Meyer, Katie A. Shin, Hocheol Sanna, Serena Pedersen, Oluf Weiss, Frank U. van der Graaf, Adriaan Jonkers, Daisy M. A. E. Fornage, Myriam Zhernakova, Daria V. Barkan, Elad Walter, Susanna Bedrani, Larbi Jørgensen, Torben Fu, Jingyuan Falony, Gwen Franke, Andre Kraaij, Robert Croitoru, Kenneth Boomsma, Dorret I. Uitterlinden, Andre G. Medina-Gomez, Carolina Claringbould, Annique Radjabzadeh, Djawad Hansen, Tue H. Lusis, Aldons J. Lerch, Markus M. Rothschild, Daphna Wijmenga, Cisca Wallen, Zachary D. Thorsen, Jonathan Bang, Corinna Võsa, Urmo Sørensen, Søren J. Tito, Raul Y. Watanabe, Kyoko Segal, Eran Shah, Shiraz A. D’Amato, Mauro Weissbrod, Omer Kim, Han-Na Spector, Tim D. Stokholm, Jakob Finnicum, Casey T. Jaddoe, Vincent W. V. Mujagic, Zlatan Bacigalupe, Rodrigo Masclee, Ad A. M. Kim, Hyung-Lae Duijts, Liesbeth Vieira-Silva, Sara Davies, Gareth E. van Duijn, Cornelia M. Qibin, Qi Le Roy, Caroline I. Moll, Henriette A. Rühlemann, Malte C. Lüll, Kreete Wade, K |
| AuthorAffiliation | 1 Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands 24 Human Genetics Center School of Public Health, The University of Texas Health Science Center at Houston, Houston, USA 6 Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 48 Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland 5 Center for Microbiology, VIB, Leuven, Belgium 43 Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands 20 Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia 22 COPSAC, Copenhagen University Hospital, Herlev-Gentofte, Copenhagen, Denmark 18 Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 2 Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands 45 Department of Pediatrics, University of Califo |
| AuthorAffiliation_xml | – name: 14 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: 56 Department of Biology, University of Copenhagen, Copenhagen, Denmark – name: 5 Center for Microbiology, VIB, Leuven, Belgium – name: 13 Laboratory of Genomic Diversity, Center for Computer Technologies, ITMO University, St. Petersburg, Russia – name: 33 Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands – name: 60 Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, the Netherlands – name: 20 Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia – name: 43 Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands – name: 48 Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland – name: 32 Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, USA – name: 17 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, USA – name: 50 Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, USA – name: 47 Center for Microbiome Innovation and department of Bioengeering, University of California San Diego, La Jolla, USA – name: 18 Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea – name: 69 School of Biological Sciences, Monash University, Clayton, Australia – name: 35 Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, the Netherlands – name: 52 Departments of Microbiology, Immunology and Molecular Genetics, and Human Genetics, University of California, Los Angeles, Los Angeles, USA – name: 29 Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, USA – name: 67 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA – name: 44 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands – name: 63 Amsterdam Public Health, Amsterdam UMC, Amsterdam, the Netherlands – name: 53 Department of Medicine, University of California, Los Angeles, Los Angles, USA – name: 72 Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Canada – name: 36 Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands – name: 7 Section of Statistical Multi-Omics, Department of Clinical & Experimental Medicine, School of Biosciences & Medicine, University of Surrey, Guildford, UK – name: 34 Nuffield Department of Population Health, University of Oxford, Oxford, UK – name: 27 Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden – name: 31 Department of Pediatrics, Albert Einstein College of Medicine, Bronx, USA – name: 28 Stress Research Institute, Stockholm University, Stockholm, Sweden – name: 16 Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany – name: 40 Department of Endocrinology, Amsterdam University Medical Center, location VUMC, Amsterdam, the Netherlands – name: 62 Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands – name: 55 Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea – name: 30 Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands – name: 65 Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, USA – name: 25 Department of Psychiatry, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands – name: 64 Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA – name: 2 Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands – name: 19 Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea – name: 41 Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK – name: 22 COPSAC, Copenhagen University Hospital, Herlev-Gentofte, Copenhagen, Denmark – name: 8 Department of Twin Research & Genetic Epidemiology, King’s College London, London, UK – name: 71 Ikerbasque, Basque Science Foundation, Bilbao, Spain – name: 39 Population Health Sciences, Bristol Medical School, Bristol, UK – name: 59 Department of gastroenterology, County Council of Östergötland, Linköping, Sweden – name: 70 Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain – name: 10 Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada – name: 12 Center for Molecular Medicine and Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden – name: 38 MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK – name: 49 Department of Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany – name: 26 Department of Neurology, University of Alabama at Birmingham, Birmingham, USA – name: 42 Centre for Clinical Research and Prevention, Bispebjerg/Frederiksberg Hospital, Capital Region of Copenhagen and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – name: 57 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany – name: 66 Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Republic of Korea – name: 1 Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands – name: 24 Human Genetics Center School of Public Health, The University of Texas Health Science Center at Houston, Houston, USA – name: 37 Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany – name: 46 Center for Microbiome Innovation, University of California San Diego, La Jolla, USA – name: 68 Istituto di Ricerca Genetica e Biomedica, National Research Council, Monserrato, Italy – name: 54 Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea – name: 21 Department of Computer Science and Cell Biology, Weizmann Institute of Science, Rehovot, Israel – name: 4 Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium – name: 11 Avera Institute of Human Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, USA – name: 61 School of Public Health, Harvard University, Boston, USA – name: 3 The Generation R Study, Erasmus MC University Medical Center, Rotterdam, the Netherlands – name: 15 Department of Medicine A, University Medicine Greifswald, Greifswald, Germany – name: 6 Institute of Microbiology, Chinese Academy of Sciences, Beijing, China – name: 23 Institute of Molecular Medicine McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA – name: 58 Department of Biomedical and Clinical Sciences, University of Linköping, Linköping, Sweden – name: 9 Department of Medicine, University of Toronto, Toronto, Canada – name: 51 Institute of Epidemiology, Kiel University, Kiel, Germany – name: 45 Department of Pediatrics, University of California San Diego, La Jolla, USA |
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Research & Genetic Epidemiology, King’s College London, Kennedy Institute of Rheumatology, University of Oxford – sequence: 48 givenname: Vincent W. V. orcidid: 0000-0003-2939-0041 surname: Jaddoe fullname: Jaddoe, Vincent W. V. organization: The Generation R Study, Erasmus MC University Medical Center, Department of Epidemiology, Erasmus MC University Medical Center – sequence: 49 givenname: Marie surname: Joossens fullname: Joossens, Marie organization: Department of Microbiology and Immunology, Rega Institute, KU Leuven, Center for Microbiology, VIB – sequence: 50 givenname: Torben surname: Jørgensen fullname: Jørgensen, Torben organization: Centre for Clinical Research and Prevention, Bispebjerg/Frederiksberg Hospital, Capital Region of Copenhagen and Faculty of Health and Medical Sciences, University of Copenhagen – sequence: 51 givenname: Daniel surname: Keszthelyi fullname: Keszthelyi, Daniel organization: Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University – sequence: 52 givenname: Rob orcidid: 0000-0002-0975-9019 surname: Knight fullname: Knight, Rob organization: Department of Pediatrics, University of California, San Diego, Center for Microbiome Innovation, University of California, San Diego, Center for Microbiome Innovation and Department of Bioengeering, University of California, San Diego – sequence: 53 givenname: Markku orcidid: 0000-0002-3394-7749 surname: Laakso fullname: Laakso, Markku organization: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland – sequence: 54 givenname: Matthias orcidid: 0000-0002-7846-955X surname: Laudes fullname: Laudes, Matthias organization: Department of Medicine I, University Hospital Schleswig-Holstein, Campus Kiel – sequence: 55 givenname: Lenore J. surname: Launer fullname: Launer, Lenore J. organization: Laboratory of Epidemiology and Population Science, National Institute on Aging – sequence: 56 givenname: Wolfgang surname: Lieb fullname: Lieb, Wolfgang organization: Institute of Epidemiology, Kiel University – sequence: 57 givenname: Aldons J. orcidid: 0000-0001-9013-0228 surname: Lusis fullname: Lusis, Aldons J. organization: Departments of Microbiology, Immunology and Molecular Genetics, and Human Genetics, University of California, Los Angeles, Department of Medicine, University of California, Los Angeles – sequence: 58 givenname: Ad A. M. surname: Masclee fullname: Masclee, Ad A. M. organization: Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University – sequence: 59 givenname: Henriette A. surname: Moll fullname: Moll, Henriette A. organization: Department of Pediatrics, Erasmus MC University Medical Center – sequence: 60 givenname: Zlatan surname: Mujagic fullname: Mujagic, Zlatan organization: Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University – sequence: 61 givenname: Qi surname: Qibin fullname: Qibin, Qi organization: Department of Epidemiology and Population Health, Albert Einstein College of Medicine – sequence: 62 givenname: Daphna orcidid: 0000-0002-0872-8624 surname: Rothschild fullname: Rothschild, Daphna organization: Department of Computer Science and Cell Biology, Weizmann Institute of Science – sequence: 63 givenname: Hocheol surname: Shin fullname: Shin, Hocheol organization: Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine – sequence: 64 givenname: Søren J. orcidid: 0000-0001-6227-9906 surname: Sørensen fullname: Sørensen, Søren J. organization: Department of Biology, University of Copenhagen – sequence: 65 givenname: Claire J. surname: Steves fullname: Steves, Claire J. organization: Department of Twin Research & Genetic Epidemiology, King’s College London – sequence: 66 givenname: Jonathan orcidid: 0000-0003-0200-0461 surname: Thorsen fullname: Thorsen, Jonathan organization: COPSAC, Copenhagen University Hospital – sequence: 67 givenname: Nicholas J. orcidid: 0000-0002-7141-9189 surname: Timpson fullname: Timpson, Nicholas J. organization: MRC Integrative Epidemiology Unit, University of Bristol, Population Health Sciences, Bristol Medical School – sequence: 69 givenname: Sara orcidid: 0000-0002-4616-7602 surname: Vieira-Silva fullname: Vieira-Silva, Sara organization: Department of Microbiology and Immunology, Rega Institute, KU Leuven, Center for Microbiology, VIB – sequence: 70 givenname: Uwe orcidid: 0000-0002-5689-3448 surname: Völker fullname: Völker, Uwe organization: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald – sequence: 71 givenname: Henry surname: Völzke fullname: Völzke, Henry organization: Institute for Community Medicine, University Medicine Greifswald – sequence: 72 givenname: Urmo orcidid: 0000-0003-3476-1652 surname: Võsa fullname: Võsa, Urmo organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 73 givenname: Kaitlin H. orcidid: 0000-0003-3362-6280 surname: Wade fullname: Wade, Kaitlin H. organization: MRC Integrative Epidemiology Unit, University of Bristol, Population Health Sciences, Bristol Medical School – sequence: 74 givenname: Susanna surname: Walter fullname: Walter, Susanna organization: Department of Biomedical and Clinical Sciences, University of Linköping, Department of Gastroenterology, County Council of Östergötland – sequence: 75 givenname: Kyoko orcidid: 0000-0002-3303-8860 surname: Watanabe fullname: Watanabe, Kyoko organization: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam – sequence: 76 givenname: Stefan orcidid: 0000-0002-3553-4315 surname: Weiss fullname: Weiss, Stefan organization: Department of Medicine A, University Medicine Greifswald, Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald – sequence: 77 givenname: Frank U. surname: Weiss fullname: Weiss, Frank U. organization: Department of Medicine A, University Medicine Greifswald – sequence: 78 givenname: Omer orcidid: 0000-0001-9860-0626 surname: Weissbrod fullname: Weissbrod, Omer organization: School of Public Health, Harvard University – sequence: 79 givenname: Harm-Jan orcidid: 0000-0001-7038-567X surname: Westra fullname: Westra, Harm-Jan organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 80 givenname: Gonneke surname: Willemsen fullname: Willemsen, Gonneke organization: Biological Psychology, Vrije Universiteit – sequence: 81 givenname: Haydeh orcidid: 0000-0001-9084-5338 surname: Payami fullname: Payami, Haydeh organization: Department of Neurology, University of Alabama at Birmingham – sequence: 82 givenname: Daisy M. A. E. surname: Jonkers fullname: Jonkers, Daisy M. A. E. organization: Division of Gastroenterology-Hepatology, Maastricht University Medical Center+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University – sequence: 83 givenname: Alejandro surname: Arias Vasquez fullname: Arias Vasquez, Alejandro organization: Department of Psychiatry, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition and Behaviour – sequence: 84 givenname: Eco J. C. surname: de Geus fullname: de Geus, Eco J. C. organization: Biological Psychology, Vrije Universiteit, Amsterdam Public Health, Amsterdam UMC – sequence: 86 givenname: Jakob orcidid: 0000-0003-4989-9769 surname: Stokholm fullname: Stokholm, Jakob organization: COPSAC, Copenhagen University Hospital – sequence: 87 givenname: Eran orcidid: 0000-0002-6859-1164 surname: Segal fullname: Segal, Eran organization: Department of Computer Science and Cell Biology, Weizmann Institute of Science – sequence: 90 givenname: Hyung-Lae surname: Kim fullname: Kim, Hyung-Lae organization: Department of Biochemistry, Ewha Womans University School of Medicine – sequence: 91 givenname: Robert C. surname: Kaplan fullname: Kaplan, Robert C. organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center – sequence: 92 givenname: Tim D. orcidid: 0000-0002-9795-0365 surname: Spector fullname: Spector, Tim D. organization: Department of Twin Research & Genetic Epidemiology, King’s College London – sequence: 93 givenname: Andre G. orcidid: 0000-0002-7276-3387 surname: Uitterlinden fullname: Uitterlinden, Andre G. organization: Department of Internal Medicine, Erasmus MC University Medical Center, The Generation R Study, Erasmus MC University Medical Center, Department of Epidemiology, Erasmus MC University Medical Center – sequence: 94 givenname: Fernando orcidid: 0000-0001-9435-9441 surname: Rivadeneira fullname: Rivadeneira, Fernando organization: Department of Internal Medicine, Erasmus MC University Medical Center, The Generation R Study, Erasmus MC University Medical Center – sequence: 95 givenname: Andre surname: Franke fullname: Franke, Andre organization: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel – sequence: 96 givenname: Markus M. orcidid: 0000-0002-9643-8263 surname: Lerch fullname: Lerch, Markus M. organization: Department of Medicine A, University Medicine Greifswald – sequence: 97 givenname: Lude surname: Franke fullname: Franke, Lude organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 98 givenname: Serena orcidid: 0000-0002-3768-1749 surname: Sanna fullname: Sanna, Serena organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Istituto di Ricerca Genetica e Biomedica, National Research Council – sequence: 99 givenname: Mauro orcidid: 0000-0003-2743-5197 surname: D’Amato fullname: D’Amato, Mauro organization: Center for Molecular Medicine and Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, School of Biological Sciences, Monash University, Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, Ikerbasque, Basque Science Foundation – sequence: 100 givenname: Oluf orcidid: 0000-0002-3321-3972 surname: Pedersen fullname: Pedersen, Oluf organization: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen – sequence: 101 givenname: Andrew D. surname: Paterson fullname: Paterson, Andrew D. organization: Genetics and Genome Biology, The Hospital for Sick Children Research Institute – sequence: 102 givenname: Robert surname: Kraaij fullname: Kraaij, Robert organization: Department of Internal Medicine, Erasmus MC University Medical Center – sequence: 103 givenname: Jeroen orcidid: 0000-0002-1337-041X surname: Raes fullname: Raes, Jeroen organization: Department of Microbiology and Immunology, Rega Institute, KU Leuven, Center for Microbiology, VIB – sequence: 104 givenname: Alexandra orcidid: 0000-0002-4574-0841 surname: Zhernakova fullname: Zhernakova, Alexandra email: sasha.zhernakova@gmail.com organization: Department of Genetics, University of Groningen, University Medical Center Groningen |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33462485$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-174837$$DView record from Swedish Publication Index (Linköpings universitet) https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-193301$$DView record from Swedish Publication Index (Stockholms universitet) http://kipublications.ki.se/Default.aspx?queryparsed=id:145699130$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 denotes shared last authorship denotes shared first authorship A.K, A.Z., R.Kr, C.M.G., L.F. and J.R. conceived and designed the study. A.K., C.M.G., R.B., D.R. and J.W. were responsible for coordinating and performing meta-analysis. A.D., C.L.R., J.A.R.G., C.T.F., X.L., D.Z., M.J.B. lead the specific downstream analyses, and should be considered as shared second authors. Specifically, A.D. performed the PheWAS analysis, C.L.R. and C.T. F. performed the heritability analysis in TwinsUK and NTR cohorts, respectively, and J.A.R.G performed the age-related analysis of LCT locus. X.L. ran and interpreted the FUMA analysis, D.Z. ran and interpreted the mendelian randomization analysis. M.J.B. substantially contributed to the development of the analysis pipeline and protocols. RK, JR and AZ jointly supervised the project. A. vd G., A.C., H.J.W., Ur.V., M.J.B., S.S. and L.F. developed the pipeline for the meta-analysis and contributed to the methodology and statistical analysis. K.W. contributed to the PheWAS enrichment analysis. A.K., C.M.G., R.B., D.R., J.W., A.D., C.L.R., J.A.R.G., C.T.F., X.L., D.Z., M.J.B., M.D.A., S.S., R.Kr., J.R. and A.Z. wrote the manuscript, with contributions from all authors. K.A.M, L.J.L and M.F collected and managed the CARDIA cohort. A.D.P, J.A.R.G., K.C., L.B. and W.T. collected and managed the GEM cohort. H.B., J.S., J.T., S.A.S, and S.J.S collected and managed the COPSAC study. D.B., O.P., T.H., T.J., and T.H.H. collected and managed the DanFunD study. D.A.H., G.F., J.R., J.W., K.H.W., M.J., N.J.T., R.Y.T., R.B. and S.V.S. collected, genotyped and managed the FGFP study. C.M.G, F.R., H.A.M., L.D. and V.W.V.J. collected and managed the Generation R study. H.N.K., H.S. and H.L.K. collected and managed the KSCS study. C.W., J.F., A.Z., L.F., S.S. and A.K. collected and managed the LLD cohort. A.J.L., E.O., K.L., M.Lk. and M.B. collected and managed the METSIM cohort. A.A.M.M., D.M.A.E.J., D.K. and Z.M. collected and managed the MIBS-CO cohort. H.P. and ZDW collected and managed the NGRC cohort. C.T.F., D.I.B., E.J.C.G., G.E.D., G.W. and R.G.I collected and managed the NTR cohort. Da.R., E.B., E.S. and O.W. collected and managed the PNP cohort. A.A., L.A., M.D.A., Su.W. and X.L. collected and managed the PopCol cohort. A.F., C.B., M.C.R., M.Ld and W.L collected and managed the BSPSPC and FOCUS cohorts. A.G.U., C.Mv.D, Dj.R. and R.Kr. collected and managed the RS cohort. F.F., F.U.W., G.H., H.V., M.M.L, St. W. and Uw.V. collected and managed the SHIP and TREND cohorts. L.Y.M., Q.Q., R.Kn., R.C.K. and R.D.B collected and managed the SOL cohort. C.I.L.R, C.J.S., J.T.B., M.A.J. and T.D.S. collected and managed the TwinsUK cohort. A.A.V. and J.S.T contributed to the discussion. All authors approved the final manuscript. Author contributions |
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| Title | Large-scale association analyses identify host factors influencing human gut microbiome composition |
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