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Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

S Fleur W Meddens, Ronald de Vlaming, Peter Bowers, Casper AP Burik, Richard Karlsson Linnér, Chanwook Lee, Aysu Okbay, Patrick Turley, Cornelius A Rietveld, Mark Alan Fontana, Mohsen Ghanbari, Fumiaki Imamura, George McMahon, Peter J van der Most, Voortman Trudy, Kaitlin H Wade, Emma L Anderson, Kim VE Braun, Pauline M Emmett, Tonũ Esko, Juan R Gonzalez, Jessica C Kiefte-de Jong, Jian’a Luan, Claudia Langenberg, Taulant Muka, Susan Ring, Fernando Rivadeneira, Josje D Schoufour, Harold Snieder, Frank JA van Rooij, Bruce HR Wolffenbuttel, 23andMe Research Team, EPIC-InterAct Consortium, Lifelines Cohort Study, George Davey Smith, Oscar H Franco, Nita G Forouhi, M Arfan Ikram, Andre G Uitterlinden, Jana V van Vliet-Ostaptchouk, Nick J Wareham, David Cesarini, K Paige Harden, James J Lee, Daniel J Benjamin, Carson C Chow, Philipp D Koellinger
doi: https://doi.org/10.1101/383406
S Fleur W Meddens
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
2Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, De Boelelaan 1085, 1081 HV, Rotterdam, The Netherlands
3Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam, 3062 PA, Rotterdam, The Netherlands
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  • For correspondence: s.f.w.meddens@vu.nl p.d.koellinger@vu.nl carsonc@niddk.nih.gov daniel.benjamin@gmail.com
Ronald de Vlaming
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
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Peter Bowers
4Department of Economics, Harvard University, Cambridge, Massachusetts 02138, USA
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Casper AP Burik
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
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Richard Karlsson Linnér
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
2Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, De Boelelaan 1085, 1081 HV, Rotterdam, The Netherlands
3Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam, 3062 PA, Rotterdam, The Netherlands
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Chanwook Lee
4Department of Economics, Harvard University, Cambridge, Massachusetts 02138, USA
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Aysu Okbay
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
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Patrick Turley
5Analytical and Translational Genetics Unit, Massachusetts General Hospital, Richard B. Simches Research building, 185 Cambridge St, CPZN-6818, Boston, MA 02114, USA
6Stanley Center for Psychiatric Genomics, The Broad Institute at Harvard and MIT, 75 Ames St, Cambridge, MA 02142, USA
7Behavioral and Health Genomics Center, Center for Economic and Social Research, University of Southern California, 635 Downey Way, Los Angeles, CA 90089, USA
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Cornelius A Rietveld
8Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, 3062 PA, Rotterdam, The Netherlands
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
3Erasmus University Rotterdam Institute for Behavior and Biology, Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam, 3062 PA, Rotterdam, The Netherlands
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Mark Alan Fontana
10Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA
11Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, 402 East 67th Street, New York, NY 10065, USA
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Mohsen Ghanbari
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
12Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Azadi Square, University Campus, 9177948564, Mashhad, Iran
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Fumiaki Imamura
13MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus Cambridge, CB2 0QQ Cambridge, United Kingdom
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George McMahon
14Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Peter J van der Most
15Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
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Voortman Trudy
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Kaitlin H Wade
14Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Emma L Anderson
14Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Kim VE Braun
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Pauline M Emmett
16Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Tonũ Esko
17Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia
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Juan R Gonzalez
18Barcelona Institute for Global Health (ISGlobal), Barcelona, 8003, Spain
19Universitat Pompeu Fabra (UPF), Barcelona, 8003, Spain
20CIBER Epidemiologí y Salud Pública (CIBERESP), Madrid, 280229, Spain
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Jessica C Kiefte-de Jong
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
21Leiden University College, Anna van Buerenplein 301, 2595 DG, Den Haag, The Netherlands
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Jian’a Luan
13MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus Cambridge, CB2 0QQ Cambridge, United Kingdom
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Claudia Langenberg
13MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus Cambridge, CB2 0QQ Cambridge, United Kingdom
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Taulant Muka
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Susan Ring
14Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Fernando Rivadeneira
22Department of Internal Medicine, Erasmus MC University Medical Center, Wytemaweg 80, Rotterdam, 3015 GE, The Netherlands
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Josje D Schoufour
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Harold Snieder
15Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
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Frank JA van Rooij
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Bruce HR Wolffenbuttel
23Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
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George Davey Smith
14Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, United Kingdom
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Oscar H Franco
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Nita G Forouhi
13MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus Cambridge, CB2 0QQ Cambridge, United Kingdom
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M Arfan Ikram
9Department of Epidemiology, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 GE, Rotterdam, The Netherlands
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Andre G Uitterlinden
22Department of Internal Medicine, Erasmus MC University Medical Center, Wytemaweg 80, Rotterdam, 3015 GE, The Netherlands
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Jana V van Vliet-Ostaptchouk
23Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
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Nick J Wareham
13MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus Cambridge, CB2 0QQ Cambridge, United Kingdom
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David Cesarini
24Department of Economics, New York University, 19 W. 4th Street, New York, NY 10012, USA
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K Paige Harden
25Department of Psychology, University of Texas at Austin, 108 E. Dean Keeton Stop #A8000, Austin, TX 78704, USA
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James J Lee
26Department of Psychology, University of Minnesota Twin Cities, 75 East River Parkway, Minneapolis, MN 55455, USA
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Daniel J Benjamin
27National Bureau of Economic Research, 1050 Massachusetts Ave, Cambridge, MA 02138, USA
7Behavioral and Health Genomics Center, Center for Economic and Social Research, University of Southern California, 635 Downey Way, Los Angeles, CA 90089, USA
28Department of Economics, University of Southern California, 635 Downey Way, Los Angeles, CA 90089, USA
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  • For correspondence: s.f.w.meddens@vu.nl p.d.koellinger@vu.nl carsonc@niddk.nih.gov daniel.benjamin@gmail.com
Carson C Chow
29Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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  • For correspondence: s.f.w.meddens@vu.nl p.d.koellinger@vu.nl carsonc@niddk.nih.gov daniel.benjamin@gmail.com
Philipp D Koellinger
1School of Business and Economics, VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands
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  • For correspondence: s.f.w.meddens@vu.nl p.d.koellinger@vu.nl carsonc@niddk.nih.gov daniel.benjamin@gmail.com
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Abstract

We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat, protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15 – 0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood poverty (|rg| ≈ 0.1 – 0.3). Overall, our results show that the relative intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations suggestive of health implications beyond caloric content.

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Genomic analysis of diet composition finds novel loci and associations with health and lifestyle
S Fleur W Meddens, Ronald de Vlaming, Peter Bowers, Casper AP Burik, Richard Karlsson Linnér, Chanwook Lee, Aysu Okbay, Patrick Turley, Cornelius A Rietveld, Mark Alan Fontana, Mohsen Ghanbari, Fumiaki Imamura, George McMahon, Peter J van der Most, Voortman Trudy, Kaitlin H Wade, Emma L Anderson, Kim VE Braun, Pauline M Emmett, Tonũ Esko, Juan R Gonzalez, Jessica C Kiefte-de Jong, Jian’a Luan, Claudia Langenberg, Taulant Muka, Susan Ring, Fernando Rivadeneira, Josje D Schoufour, Harold Snieder, Frank JA van Rooij, Bruce HR Wolffenbuttel, 23andMe Research Team, EPIC-InterAct Consortium, Lifelines Cohort Study, George Davey Smith, Oscar H Franco, Nita G Forouhi, M Arfan Ikram, Andre G Uitterlinden, Jana V van Vliet-Ostaptchouk, Nick J Wareham, David Cesarini, K Paige Harden, James J Lee, Daniel J Benjamin, Carson C Chow, Philipp D Koellinger
bioRxiv 383406; doi: https://doi.org/10.1101/383406
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Genomic analysis of diet composition finds novel loci and associations with health and lifestyle
S Fleur W Meddens, Ronald de Vlaming, Peter Bowers, Casper AP Burik, Richard Karlsson Linnér, Chanwook Lee, Aysu Okbay, Patrick Turley, Cornelius A Rietveld, Mark Alan Fontana, Mohsen Ghanbari, Fumiaki Imamura, George McMahon, Peter J van der Most, Voortman Trudy, Kaitlin H Wade, Emma L Anderson, Kim VE Braun, Pauline M Emmett, Tonũ Esko, Juan R Gonzalez, Jessica C Kiefte-de Jong, Jian’a Luan, Claudia Langenberg, Taulant Muka, Susan Ring, Fernando Rivadeneira, Josje D Schoufour, Harold Snieder, Frank JA van Rooij, Bruce HR Wolffenbuttel, 23andMe Research Team, EPIC-InterAct Consortium, Lifelines Cohort Study, George Davey Smith, Oscar H Franco, Nita G Forouhi, M Arfan Ikram, Andre G Uitterlinden, Jana V van Vliet-Ostaptchouk, Nick J Wareham, David Cesarini, K Paige Harden, James J Lee, Daniel J Benjamin, Carson C Chow, Philipp D Koellinger
bioRxiv 383406; doi: https://doi.org/10.1101/383406

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