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New genetic loci link adipose and insulin biology to body fat distribution
Open accessAbstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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“Interestingly, although Gao et al. use the most up-to-date BMI GWAS data, 20 they do not do the same for WHR, despite the most recent GWAS for WHR adjusted for BMI identifying 33 additional variants (as well as confirming the 14 used here from the earlier GWAS) and being published around the same time as the most up-to-date BMI GWAS.”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [21]
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“In both GWAS, the results of the per allele effect of the genetic instrument on WHR adjusted for BMI is notably stronger in females than males.”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [21]
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“Seven of the 14 WHR adjusted for BMI variants used by Gao and colleagues were stronger in females compared with males ( Table 2 ), with 19 of the 44 variants in the more up-to-date GWAS being stronger in females (and one stronger in males).”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [21]
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BackgroundSelf-citationPCA-based GRS analysis enhances the effectiveness for genetic correlation detection
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“Other genes in this region have also been implicated in differential adipose deposition (LARGE [78] and HMGXB4 [34]) and fat mass (near ODF3B) [25], and electronic medical recorddefined BMI in children (APOL5) [79], suggesting that our study has detected a biological relationship with energy balance or storage in this…”
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p53 target ANKRA2 cooperates with RFX7 to regulate tumor suppressor genes
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“BMI and WHR (adjusted for BMI) associated genetic variants were sourced from GIANT consortium 24,25 .”
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“We also incorporated WC-related exposure data from studies by Shungin et al and Mbatchou et al 31,32 Finally, we included data on smoking and drinking from the GWAS and Sequencing Consortium of Alcohol and Nicotine use.”
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“LOF variants in INSR , ACVR1C (including 2:157,550,353:A:G), PDE3B (including 11:14,843,853:C:T), and INHBE were associated with decreased WHRadjBMI [57–59], while a SMAD6 variant was associated with increased WHRadjBMI [60].”
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Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study
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Self-citationPerceived neighborhood social cohesion and cardiometabolic risk: a gene × environment study
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“The BMI and WHR polygenic scores represent distinct genetic components, and are also associated with multiple other metabolic traits (Locke et al. 2015; Shungin et al. 2015).”
InfluentialRisk factors for insulin resistance in midlife Singaporean women
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“Over the past decade, genome-wide association studies have successfully identified numerous common variants associated with obesity-related traits, such as BMI, waist to hip ratio, and body fat index (7-9).”
BackgroundA genome-wide methylation study of body fat traits in the Norfolk Island isolate
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“The study Mora-García et al. showed shown there was significant association between rs 926,198 and WHR but there was no association between rs 926198 and WC and WHtR [31].”
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“…of obesity on HbA1c are different in patients with CHD and the general population We use GWAS summary data on BMI [27], WHR and WHRadjBMI [28] for European descent from the Genetic Investigation of ANthropometric Traits (GIANT) by GWAS meta-analyses of 339,224 and 224,459 individuals,…”
Shared genetic loci for body fat storage and adipocyte lipolysis in humans
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“proposed GRB14, but also Cordon-Bleu WH2 Repeat Protein Like 1 (COBLL1) as potential candidate gene affected by the WHR-associated SNPs in 2015 [8].”
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“This provided a set of genes with evidence of regulatory relationships to SNVs previously associated with anthropometry traits.(6,7,9) We hypothesized that if the expression of these genes is involved in the causal mechanism of these”
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“This GWAS comprised 188,577 individuals, 95% of whom were Europeans.”
MethodDeep subcutaneous adipose tissue lipid unsaturation associates with intramyocellular lipid content
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Self-citationNontrivial Replication of Loci Detected by Multi-Trait Methods
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Self-citationTrefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target
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Metadata
- Authors
- The ADIPOGen Consortium, Shungin, D., The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The, G. L. G. C., The, I. C. B. P., The International Endogene Consortium, Study, T. L. C., The MAGIC Investigators, The MuTHER Consortium, The PAGE Consortium, The ReproGen Consortium, Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Locke, A. E., Mägi, R., Strawbridge, R. J., Pers, T. H., Fischer, K., Justice, A. E., Workalemahu, T., Wu, J. M. W., Buchkovich, M. L., Heard-Costa, N. L., Roman, T. S., Drong, A. W., Song, C., Gustafsson, S., Day, F. R., Esko, T., Fall, T., Kutalik, Z., Luan, J., Randall, J. C., Scherag, A., Vedantam, S., Wood, A. R., Chen, J., Fehrmann, R., Karjalainen, J., Kahali, B., Liu, C.-T., Schmidt, E. M., Absher, D., Amin, N., Anderson, D., Beekman, M., Bragg-Gresham, J. L., Buyske, S., Demirkan, A., Ehret, G. B., Feitosa, M. F., Goel, A., Jackson, A. U., Johnson, T., Kleber, M. E., Kristiansson, K., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Palmer, C. D., Pasko, D., Pechlivanis, S., Peters, M. J., Prokopenko, I., Stančáková, A., Ju Sung, Y., Tanaka, T., Teumer, A., Van Vliet-Ostaptchouk, J. V., Yengo, L., Zhang, W., Albrecht, E., Ärnlöv, J., Arscott, G. M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A. J., Berne, C., Blüher, M., Böhringer, S., Bonnet, F., Böttcher, Y., Bruinenberg, M., Carba, D. B., Caspersen, I. H., Clarke, R., Warwick Daw, E., Deelen, J., Deelman, E., Delgado, G., Doney, A. S. F., Eklund, N., Erdos, M. R., Estrada, K., Eury, E., Friedrich, N., Garcia, M. E., Giedraitis, V., Gigante, B., Go, A. S., Golay, A., Grallert, H., Grammer, T. B., Gräßler, J., Grewal, J., Groves, C. J., Haller, T., Hallmans, G., Hartman, C. A., Hassinen, M., Hayward, C., Heikkilä, K., Herzig, K.-H., Helmer, Q., Hillege, H. L., Holmen, O., Hunt, S. C., Isaacs, A., Ittermann, T., James, A. L., Johansson, I., Juliusdottir, T., Kalafati, I.-P., Kinnunen, L., Koenig, W., Kooner, I. K., Kratzer, W., Lamina, C., Leander, K., Lee, N. R., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Mach, F., Magnusson, P. K. E., Mahajan, A., McArdle, W. L., Menni, C., Merger, S., Mihailov, E., Milani, L., Mills, R., Moayyeri, A., Monda, K. L., Mooijaart, S. P., Mühleisen, T. W., Mulas, A., Müller, G., Müller-Nurasyid, M., Nagaraja, R., Nalls, M. A., Narisu, N., Glorioso, N., Nolte, I. M., Olden, M., Rayner, N. W., Renstrom, F., Ried, J. S., Robertson, N. R., Rose, L. M., Sanna, S., Scharnagl, H., Scholtens, S., Sennblad, B., Seufferlein, T., Sitlani, C. M., Vernon Smith, A., Stirrups, K., Stringham, H. M., Sundström, J., Swertz, M. A., Swift, A. J., Syvänen, A.-C., Tayo, B. O., Thorand, B., Thorleifsson, G., Tomaschitz, A., Troffa, C., van Oort, F. V. A., Verweij, N., Vonk, J. M., Waite, L. L., Wennauer, R., Wilsgaard, T., Wojczynski, M. K., Wong, A., Zhang, Q., Hua Zhao, J., Brennan, E. P., Choi, M., Eriksson, P., Folkersen, L., Franco-Cereceda, A., Gharavi, A. G., Hedman, Å. K., Hivert, M.-F., Huang, J., Kanoni, S., Karpe, F., Keildson, S., Kiryluk, K., Liang, L., Lifton, R. P., Ma, B., McKnight, A. J., McPherson, R., Metspalu, A., Min, J. L., Moffatt, M. F., Montgomery, G. W., Murabito, J. M., Nicholson, G., Nyholt, D. R., Olsson, C., Perry, J. R. B., Reinmaa, E., Salem, R. M., Sandholm, N., Schadt, E. E., Scott, R. A., Stolk, L., Vallejo, E. E., Westra, H.-J., Zondervan, K. T., Amouyel, P., Arveiler, D., Bakker, S. J. L., Beilby, J., Bergman, R. N., Blangero, J., Brown, M. J., Burnier, M., Campbell, H., Chakravarti, A., Chines, P. S., Claudi-Boehm, S., Collins, F. S., Crawford, D. C., Danesh, J., de Faire, U., de Geus, E. J. C., Dörr, M., Erbel, R., Eriksson, J. G., Farrall, M., Ferrannini, E., Ferrières, J., Forouhi, N. G., Forrester, T., Franco, O. H., Gansevoort, R. T., Gieger, C., Gudnason, V., Haiman, C. A., Harris, T. B., Hattersley, A. T., Heliövaara, M., Hicks, A. A., Hingorani, A. D., Hoffmann, W., Hofman, A., Homuth, G., Humphries, S. E., Hyppönen, E., Illig, T., Jarvelin, M.-R., Johansen, B., Jousilahti, P., Jula, A. M., Kaprio, J., Kee, F., Keinanen-Kiukaanniemi, S. M., Kooner, J. S., Kooperberg, C., Kovacs, P., Kraja, A. T., Kumari, M., Kuulasmaa, K., Kuusisto, J., Lakka, T. A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lyssenko, V., Männistö, S., Marette, A., Matise, T. C., McKenzie, C. A., McKnight, B., Musk, A. W., Möhlenkamp, S., Morris, A. D., Nelis, M., Ohlsson, C., Oldehinkel, A. J., Ong, K. K., Palmer, L. J., Penninx, B. W., Peters, A., Pramstaller, P. P., Raitakari, O. T., Rankinen, T., Rao, D. C., Rice, T. K., Ridker, P. M., Ritchie, M. D., Rudan, I., Salomaa, V., Samani, N. J., Saramies, J., Sarzynski, M. A., Schwarz, P. E. H., Shuldiner, A. R., Staessen, J. A., Steinthorsdottir, V., Stolk, R. P., Strauch, K., Tönjes, A., Tremblay, A., Tremoli, E., Vohl, M.-C., Völker, U., Vollenweider, P., Wilson, J. F., Witteman, J. C., Adair, L. S., Bochud, M., Boehm, B. O., Bornstein, S. R., Bouchard, C., Cauchi, S., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Cooper, R. S., Dedoussis, G., Ferrucci, L., Froguel, P., Grabe, H.-J., Hamsten, A., Hui, J., Hveem, K., Jöckel, K.-H., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., März, W., Munroe, P. B., Njølstad, I., Oostra, B. A., Palmer, C. N. A., Pedersen, N. L., Perola, M., Pérusse, L., Peters, U., Power, C., Quertermous, T., Rauramaa, R., Rivadeneira, F., Saaristo, T. E., Saleheen, D., Sinisalo, J., Eline Slagboom, P., Snieder, H., Spector, T. D., Thorsteinsdottir, U., Stumvoll, M., Tuomilehto, J., Uitterlinden, A. G., Uusitupa, M., van der Harst, P., Veronesi, G., Walker, M., Wareham, N. J., Watkins, H., Wichmann, H.-E., Abecasis, G. R., Assimes, T. L., Berndt, S. I., Boehnke, M., Borecki, I. B., Deloukas, P., Franke, L., Frayling, T. M., Groop, L. C., Hunter, D. J., Kaplan, R. C., O’Connell, J. R., Qi, L., Schlessinger, D., Strachan, D. P., Stefansson, K., van Duijn, C. M., Willer, C. J., Visscher, P. M., Yang, J., Hirschhorn, J. N., Carola Zillikens, M., McCarthy, M. I., Speliotes, E. K., North, K. E., Fox, C. S., Barroso, I., Franks, P. W., Ingelsson, E., Heid, I. M., Loos, R. J. F., Cupples, L. A., Morris, A. P., Lindgren, C. M., & Mohlke, K. L.
- Affiliations
- Lund University (SE)
- University of Regensburg (DE)
- Brigham and Women's Hospital (US)
- University Medical Center Groningen (NL)
- University of Michigan (US)
- Centre for Human Genetics (GB)
- Boston Children's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Harvard University (US)
- Broad Institute (US)
- Boston University (US)
- Uppsala University (SE)
- University of Cambridge (GB)
- SIB Swiss Institute of Bioinformatics (CH)
- University of Exeter (GB)
- Rutgers, The State University of New Jersey (US)
- The Kids Research Institute Australia (AU)
- Johns Hopkins University (US)
- Washington University in St. Louis (US)
- King's College London (GB)
- Heidelberg University (DE)
- University of Eastern Finland (FI)
- Erasmus MC (NL)
- National Institute on Aging (US)
- Universitätsmedizin Greifswald (DE)
- Centre National de la Recherche Scientifique (FR)
- Azienda Sanitaria di Firenze (IT)
- Helmholtz Munich (DE)
- Dalarna University (SE)
- University of Oxford (GB)
- Texas Biomedical Research Institute (US)
- Inserm (FR)
- Leiden University Medical Center (NL)
- University of Southern California (US)
- University of Helsinki (FI)
- National Institutes of Health (US)
- Kaiser Permanente (US)
- University Hospital of Geneva (CH)
- University Hospital Carl Gustav Carus (DE)
- Western General Hospital (GB)
- University of Utah (US)
- Norwegian University of Science and Technology (NO)
- The University of Western Australia (AU)
- University Hospital Ulm (DE)
- Harokopio University of Athens (GR)
- Innsbruck Medical University (AT)
- Ealing Hospital NHS Trust (GB)
- Karolinska Institutet (SE)
- University of Bristol (GB)
- University of Bonn (DE)
- University of Sassari (IT)
- Medical University of Graz (AT)
- Institute of Genetic and Biomedical Research (IT)
- University of Washington (US)
- Science for Life Laboratory (SE)
- MRC Unit for Lifelong Health and Ageing (GB)
- University College Dublin (IE)
- Seoul National University (KR)
- Shanghai Jiao Tong University (CN)
- Queen Mary University of London (GB)
- Howard Hughes Medical Institute (US)
- Queen's University Belfast (GB)
- QIMR Berghofer Medical Research Institute (AU)
- National Heart, Lung, and Blood Institute (US)
- Helsinki University Hospital (FI)
- Université de Strasbourg (FR)
- Cedars-Sinai Medical Center (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Vanderbilt University (US)
- University of Pisa (IT)
- Essen University Hospital (DE)
- University of the West Indies (JM)
- University of Iceland (IS)
- Eurac Research (IT)
- University College London (GB)
- University of South Australia (AU)
- Finnish Institute for Health and Welfare (FI)
- Imperial College Healthcare NHS Trust (GB)
- Tampere University (FI)
- Steno Diabetes Centers (DK)
- Sir Charles Gairdner Hospital (AU)
- University of Dundee (GB)
- University of Toronto (CA)
- Vrije Universiteit Amsterdam (NL)
- Ontario Institute for Cancer Research (CA)
- Pennington Biomedical Research Center (US)
- Pennsylvania State University (US)
- University of Maryland, Baltimore (US)
- Maastricht University (NL)
- University of Milan (IT)
- Nanyang Technological University (SG)
- Université de Lille (FR)
- University of London (GB)
- Loyola University Chicago (US)
- Institut für Medizinische Informatik, Biometrie und Epidemiologie (DE)
- Wake Forest University Health Sciences (US)
- Finnish Diabetes Association (FI)
- deCODE Genetics (Iceland) (IS)
- University of Insubria (IT)
- Albert Einstein College of Medicine (US)
- The University of Queensland (AU)
- Corresponding author
- Lindgren, Cecilia M.
- Mohlke, Karen L
- ORCID
- Shungin, Dmitry
- Winkler, Thomas W.
- Ferreira, Teresa
- Locke, Adam E.
- Mägi, Reedik
- Strawbridge, Rona J.
- Pers, Tune H.
- Fischer, Krista
- Justice, Anne E.
- Workalemahu, Tsegaselassie
- Wu, Joseph M. W.
- Buchkovich, Martin L.
- Roman, Tamara S.
- Song, Ci
- Gustafsson, Stefan
- Day, Felix R.
- Fall, Tove
- Kutalik, Zoltán
- Luan, Jian’an
- Scherag, André
- Vedantam, Sailaja
- Wood, Andrew R.
- Fehrmann, Rudolf
- Karjalainen, Juha
- Kahali, Bratati
- Schmidt, Ellen M.
- Amin, Najaf
- Anderson, Denise
- Beekman, Marian
- Buyske, Steven
- Ehret, Georg B.
- Feitosa, Mary F.
- Goel, Anuj
- Jackson, Anne U.
- Johnson, Toby
- Kleber, Marcus E.
- Kristiansson, Kati
- Mangino, Massimo
- Palmer, Cameron D.
- Pechlivanis, Sonali
- Peters, Marjolein J.
- Prokopenko, Inga
- Tanaka, Toshiko
- Teumer, Alexander
- Yengo, Loïc
- Zhang, Weihua
- Ärnlöv, Johan
- Arscott, Gillian M.
- Bandinelli, Stefania
- Bellis, Claire
- Bennett, Amanda J.
- Blüher, Matthias
- Böhringer, Stefan
- Bonnet, Fabrice
- Böttcher, Yvonne
- Carba, Delia B.
- Caspersen, Ida H.
- Deelen, Joris
- Deelman, Ewa
- Doney, Alex S. F.
- Erdos, Michael R.
- Estrada, Karol
- Giedraitis, Vilmantas
- Gigante, Bruna
- Go, Alan S.
- Golay, Alain
- Grallert, Harald
- Grewal, Jagvir
- Groves, Christopher J.
- Haller, Toomas
- Hartman, Catharina A.
- Hayward, Caroline
- Herzig, Karl-Heinz
- Hillege, Hans L.
- Hunt, Steven C.
- Isaacs, Aaron
- Ittermann, Till
- Johansson, Ingegerd
- Kalafati, Ioanna-Panagiota
- Kinnunen, Leena
- Kratzer, Wolfgang
- Lamina, Claudia
- Leander, Karin
- Lichtner, Peter
- Lind, Lars
- Lindström, Jaana
- Lorentzon, Mattias
- Mach, François
- Magnusson, Patrik K. E.
- Mahajan, Anubha
- Menni, Cristina
- Merger, Sigrun
- Milani, Lili
- Mills, Rebecca
- Moayyeri, Alireza
- Mooijaart, Simon P.
- Mulas, Antonella
- Müller, Gabriele
- Nagaraja, Ramaiah
- Narisu, Narisu
- Nolte, Ilja M.
- Olden, Matthias
- Rayner, Nigel W.
- Rose, Lynda M.
- Sanna, Serena
- Scharnagl, Hubert
- Scholtens, Salome
- Sennblad, Bengt
- Seufferlein, Thomas
- Sitlani, Colleen M.
- Stirrups, Kathleen
- Stringham, Heather M.
- Sundström, Johan
- Swertz, Morris A.
- Tayo, Bamidele O.
- Thorand, Barbara
- Tomaschitz, Andreas
- Verweij, Niek
- Vonk, Judith M.
- Wilsgaard, Tom
- Wojczynski, Mary K.
- Wong, Andrew
- Brennan, Eoin P.
- Choi, Murim
- Eriksson, Per
- Folkersen, Lasse
- Gharavi, Ali G.
- Hedman, Åsa K.
- Hivert, Marie-France
- Huang, Jinyan
- Kanoni, Stavroula
- Karpe, Fredrik
- Kiryluk, Krzysztof
- Liang, Liming
- Lifton, Richard P.
- Ma, Baoshan
- McKnight, Amy J.
- McPherson, Ruth
- Metspalu, Andres
- Min, Josine L.
- Moffatt, Miriam F.
- Montgomery, Grant W.
- Murabito, Joanne M.
- Nyholt, Dale R.
- Olsson, Christian
- Perry, John R. B.
- Salem, Rany M.
- Sandholm, Niina
- Vallejo, Edgar E.
- Westra, Harm-Jan
- Zondervan, Krina T.
- Amouyel, Philippe
- Bakker, Stephan J. L.
- Beilby, John
- Bergman, Richard N.
- Blangero, John
- Brown, Morris J.
- Burnier, Michel
- Chakravarti, Aravinda
- Collins, Francis S.
- Crawford, Dana C.
- Danesh, John
- Dörr, Marcus
- Eriksson, Johan G.
- Farrall, Martin
- Ferrannini, Ele
- Ferrières, Jean
- Forouhi, Nita G.
- Franco, Oscar H.
- Gansevoort, Ron T.
- Gieger, Christian
- Gudnason, Vilmundur
- Haiman, Christopher A.
- Harris, Tamara B.
- Hattersley, Andrew T.
- Hicks, Andrew A.
- Hingorani, Aroon D.
- Hoffmann, Wolfgang
- Homuth, Georg
- Humphries, Steve E.
- Hyppönen, Elina
- Johansen, Berit
- Kaprio, Jaakko
- Kee, Frank
- Keinanen-Kiukaanniemi, Sirkka M.
- Kooner, Jaspal S.
- Kooperberg, Charles
- Kovacs, Peter
- Kuulasmaa, Kari
- Lakka, Timo A.
- Langenberg, Claudia
- Lehtimäki, Terho
- Lyssenko, Valeriya
- Männistö, Satu
- Marette, André
- Matise, Tara C.
- Musk, Arthur W.
- Morris, Andrew D.
- Nelis, Mari
- Ohlsson, Claes
- Oldehinkel, Albertine J.
- Ong, Ken K.
- Palmer, Lyle J.
- Penninx, Brenda W.
- Peters, Annette
- Pramstaller, Peter P.
- Raitakari, Olli T.
- Rao, D. C.
- Rice, Treva K.
- Ridker, Paul M.
- Ritchie, Marylyn D.
- Rudan, Igor
- Salomaa, Veikko
- Samani, Nilesh J.
- Sarzynski, Mark A.
- Schwarz, Peter E. H.
- Shuldiner, Alan R.
- Staessen, Jan A.
- Stolk, Ronald P.
- Strauch, Konstantin
- Tönjes, Anke
- Tremblay, Angelo
- Tremoli, Elena
- Vohl, Marie-Claude
- Völker, Uwe
- Wilson, James F.
- Adair, Linda S.
- Bochud, Murielle
- Boehm, Bernhard O.
- Bornstein, Stefan R.
- Bouchard, Claude
- Cauchi, Stéphane
- Caulfield, Mark J.
- Chambers, John C.
- Chasman, Daniel I.
- Cooper, Richard S.
- Dedoussis, George
- Ferrucci, Luigi
- Froguel, Philippe
- Grabe, Hans-Jörgen
- Hamsten, Anders
- Hui, Jennie
- Hveem, Kristian
- Jöckel, Karl-Heinz
- Kuh, Diana
- Laakso, Markku
- März, Winfried
- Munroe, Patricia B.
- Njølstad, Inger
- Pedersen, Nancy L.
- Perola, Markus
- Peters, Ulrike
- Power, Chris
- Quertermous, Thomas
- Rivadeneira, Fernando
- Saleheen, Danish
- Sinisalo, Juha
- Snieder, Harold
- Spector, Tim D.
- Tuomilehto, Jaakko
- Uitterlinden, André G.
- Uusitupa, Matti
- Veronesi, Giovanni
- Walker, Mark
- Wareham, Nicholas J.
- Watkins, Hugh
- Wichmann, H-Erich
- Assimes, Themistocles L.
- Berndt, Sonja I.
- Boehnke, Michael
- Borecki, Ingrid B.
- Deloukas, Panos
- Franke, Lude
- Frayling, Timothy M.
- Kaplan, Robert C.
- O’Connell, Jeffrey R.
- Qi, Lu
- Strachan, David P.
- Willer, Cristen J.
- Visscher, Peter M.
- Yang, Jian
- Hirschhorn, Joel N.
- McCarthy, Mark I.
- Speliotes, Elizabeth K.
- North, Kari E.
- Fox, Caroline S.
- Barroso, Inês
- Franks, Paul W.
- Ingelsson, Erik
- Heid, Iris M.
- Loos, Ruth J. F.
- Cupples, L. Adrienne
- Morris, Andrew P.
- Lindgren, Cecilia M.
- Mohlke, Karen L
- Venue
- Nature
- Published
- 2015-02-11
- Volume
- 518
- Issue
- 7538
- Pages
- 187-196
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4338562
- OpenAlex
- W2047783882
- Cited by
- 1,580
- References
- 101
- Citations by year
- 2026: 56 · 2025: 120 · 2024: 129 · 2023: 177 · 2022: 158 · 2021: 167 · 2020: 122 · 2019: 142 · 2018: 161 · 2017: 156 · 2016: 118 · 2015: 71
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Research Explorer (The University of Manchester) (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
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- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- VU Research Portal (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Civil War Book Review (submittedVersion)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
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- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
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- Open Research Exeter (University of Exeter) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
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- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
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- UniSA Research Outputs Repository (University of South Australia) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- BCU Open Access Repository (Birmingham City University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- McKnight Foundation
- Pennsylvania State University (16802)
- Wellcome Trust (098017, 098381, 098498, 085235, 097117, WT098017, 100574, 084766, WT098381, WT100574, WT097117, WT084766, WT098498, WT085235)
- Cancer Research UK (CRUK_14136, 14136)
- National Institute for Health and Care Research (NF-SI-0512-10165, NF-SI-0513-10109, NF-SI-0611-10170, NF-SI-0512-10113, NF-SI-0508-10082, NF-SI-0507-10380, NF-SI-0611-10099, NF-SI-0512-10114, NF-SI-0611-10219, NF-SI-0513-10085, NF-SI-0514-10027, NF-SI-0512-10135)
- British Heart Foundation (BHF_FS/14/55/30806, FS/14/55/30806, BHF_RG/13/2/30098, RG/08/008/25291, BHF_RG/10/12/28456, BHF_RG/08/008/25291, RG/10/12/28456, BHF_RG/08/014/24067, RG/13/2/30098, RG/07/008/23674, RG/08/014/24067)
- Diabetes UK (DUK_12/0004470, 12/0004470)
- University of Leicester
- University of Warwick
- European Commission (259679)
- Vrije Universiteit Amsterdam
- Bundesministerium für Bildung und Forschung (01EO1001)
- Lundbeckfonden (R190 2014-3904)
- Turun Yliopisto
- Novo Nordisk Fonden (NNF14OC0010513, NNF12OC1016467, NNF13OC0005785, NNF15OC0016416, NNF14OC0011039, NNF13OC0005781, NNF12OC1016167, NNF11OC1014855)
- Turun Yliopistollinen Keskussairaala
- National Institutes of Health (1r01hl120393-01a1)
- Medical Research Council (MC_U106179472, MR/K013351/1, MR/K006584/1, MC_UU_12015/5, MR/N01104X/1, MC_PC_U127561128, MR/L003120/1, MR/K011480/1, MC_UP_A100_1003, MC_UU_12015/2, G0601261, MC_UP_A620_1014, G0601463, MC_UU_12011/1, MC_UU_12015/1, G1000143, G1001799)
- Economic and Social Research Council (ES/J023299/1, ES/F02679X/1)
- National Institute on Aging (U01AG049505, R01AG025941, R01AG033193, R01AG041517)
- National Heart, Lung, and Blood Institute (R00HL094535, R01-HL120393, R01HL105756, K01HL116770, R01HL117078, R01HL117626, T32HL069768, T32HL007055, R01HL109946)
- National Institute on Drug Abuse (R21DA027040)
- National Human Genome Research Institute (Z01HG000024, U01HG007416, U01HG007417, U01HG007419, U01HG007376)
- National Cancer Institute (UM1CA182913, UM1CA182910, P30CA071789)
- National Institute of General Medical Sciences (T32GM007092, T32GM067553, P30GM103341)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078150, R01DK072193, R01DK089256, U01DK062370, R01DK107437, K23DK080145, P30DK079637, P30DK072488, P60DK020541, R01DK075787, P30DK020572, P30DK056341, R01DK093757, P30DK020541, P30DK040561, R01DK062370)
- NIH Clinical Center
- National Institute on Minority Health and Health Disparities (P20MD006899)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083211)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- body fat distribution, waist-to-hip ratio, waist circumference, hip circumference, genetic loci, adipose tissue, adipogenesis, angiogenesis, insulin resistance, transcriptional regulation, sexual dimorphism, abdominal fat, cardiometabolic traits, regulatory elements
- MeSH terms
- Adipose Tissue, Age Factors, Europe, Female, Humans, Insulin, Insulin Resistance, Male, Models, Biological, Obesity, Sex Characteristics, Transcription, Genetic, Genome, Human, Body Mass Index, Adipocytes, Neovascularization, Physiologic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Epigenesis, Genetic, Racial Groups, Waist-Hip Ratio, Adipogenesis, Body Fat Distribution, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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