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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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Enhancing adipose tissue plasticity: progenitor cell roles in metabolic health
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Chesi, A., Mitchell, J. A., Kalkwarf, H. J., Bradfield, J. P., Lappe, J. M., Cousminer, D. L., Roy, S. M., McCormack, S. E., Gilsanz, V., Oberfield, S. E., et al. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3097 · Cited by 39
“The signals identified in this study do not reside in the X chromosome, adding to the mounting evidence for autosomal sex-specific effects that recent GWAS have begun to uncover for different traits (cardiac diseases–related and anthropometric traits,((47,48)) type II diabetes,((49)) and asthma((50))).”
BackgroundBagchi, D. P., Li, Z., Corsa, C. A. S., Hardij, J., Mori, H., Learman, B. S., Lewis, K. T., Schill, R. L., Romanelli, S. M., & MacDougald, O. A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.100992 · Cited by 38
“Common variants in Wnt signaling inhibitor ZNRF3 and Wnt signaling activator RSPO3 are associated with increased waist-to-hip ratio [25 e 27].”
Genetics of Diabetic Nephropathy: a Long Road of Discovery
McKnight, A. J., Duffy, S., & Maxwell, A. P. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0610-9 · Cited by 40
Self-citationNutritional Regulation of Human Brown Adipose Tissue
Suchacki, K. J., & Stimson, R. H. (2021) · Nutrients · doi:10.3390/nu13061748 · Cited by 45
“Brown adipose tissue (BAT), white adipose tissue (WAT), Body mass index (BMI), waist-hip-ratio (WHR).”
BackgroundIdentification of TBX15 as an adipose master trans regulator of abdominal obesity genes
Pan, D. Z., Miao, Z., Comenho, C., Rajkumar, S., Koka, A., Lee, S. H., Alvarez, M., Kamińska, D., Ko, A., Sinsheimer, J. S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00939-2 · Cited by 40
“Furthermore, while overall obesity measures like BMI do not exhibit sexual dimorphism [8], WHRadjBMI and fat distribution have clear sexspecific differences that are reflected in differences in heritability [8, 15], GWAS loci [13, 74], and ultimately in risk for disease outcomes such as T2D and cardiovascu-”
BackgroundMethodInfluentialSelf-citationEmdin, C. A., Haas, M., Khera, A. V., Aragam, K. G., Chaffin, M. D., Jiang, L., Wei, W., Feng, Q., Karjalainen, J. M., Havulinna, A. S., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/594523 · Cited by 40
Self-citationPrediction of type 2 diabetes mellitus onset using logistic regression-based scorecards
Edlitz, Y., & Segal, E. (2022) · eLife · doi:10.7554/elife.71862 · Cited by 43
Genetics of sexually dimorphic adipose distribution in humans
Hansen, G. T., Sobreira, D. R., Weber, Z., Thornburg, A. G., Aneas, I., Zhang, L., Sakabe, N. J., Joslin, A. C., Haddad, G. A., Strobel, S., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01306-0 · Cited by 38
“Non-modifiable” Risk Factors for Periodontitis and Diabetes
Borgnakke, W. S. (2016) · Current Oral Health Reports · doi:10.1007/s40496-016-0098-7 · Cited by 44
Borges, M. C., Oliveira, I. O., Freitas, D. F., Horta, B. L., Ong, K. K., Gigante, D. P., & Barros, A. J. D. (2017) · International Journal of Epidemiology · doi:10.1093/ije/dyx022 · Cited by 39
“randomization analysis The Genetic Investigation of ANthropometric Traits (GIANT) consortium included up to 210 088 individuals of European ancestry from cohorts genotyped with genome-wide single nucleotide polymorphism (SNP) arrays (n1⁄4 57) or Metabochip (n1⁄4 44).(17) Estimates of SNP-waist circumference or SNP-hip…”
MethodSelf-citationCatching new targets in metabolic disease with a zebrafish
Kamel, M., & Ninov, N. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.08.007 · Cited by 39
Bradford, S. T., Nair, S. S., Statham, A. L., van Dijk, S. J., Peters, T. J., Anwar, F., French, H. J., von Martels, J. Z. H., Sutcliffe, B., Maddugoda, M. P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45777-w · Cited by 38
Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer
Heo, J.-W., Kim, S., & Sung, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031253 · Cited by 43
Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress
Coronel, L., Riege, K., Schwab, K., Förste, S., Häckes, D., Semerau, L., Bernhart, S. H., Siebert, R., Hoffmann, S., & Fischer, M. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab575 · Cited by 39
“neoplasms, RFX7 has been associated with body fat distribution (13), Alzheimer’s disease 51”
BackgroundTelomere length and metabolic syndrome traits: A Mendelian randomisation study
Loh, N. Y., Noordam, R., & Christodoulides, C. (2021) · Aging Cell · doi:10.1111/acel.13445 · Cited by 39
Mao, X., Mao, S.-H., Sun, H., Huang, F., Wang, Y., Zhang, D., Wang, Q., Li, Z., Zou, W., & Liao, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1091780 · Cited by 39
“GWAS summary statistics for hip circumference, waist circumference and waist-to-hip ratio were extracted from the GIANT (Genetic Investigation of ANthropometric Traits) consortium (26).”
MethodGibson, M., Lawlor, D. A., & Millard, L. A. C. (2023) · BMC Medicine · doi:10.1186/s12916-023-02832-8 · Cited by 43
CCDC92 deficiency ameliorates podocyte lipotoxicity in diabetic kidney disease
Zuo, F., Wang, Y., Xu, X., Ding, R., Tang, W., Sun, Y., Wang, X., Zhang, Y., Wu, J., Xie, Y., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155724 · Cited by 44
Self-citationViitasalo, A., Schnurr, T. M., Pitkänen, N., Hollensted, M., Nielsen, T. R. H., Pahkala, K., Atalay, M., Lind, M. V., Heikkinen, S., Frithioff‐Bøjsøe, C., et al. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz187 · Cited by 38
“When using a genetic risk score (GRS) comprising 48 known variants for waist-to-hip ratio (WHR) adjusted for BMI (WHRadjBMI) (7), a genetically instrumented increase in WHRadjBMI was associated with higher concentrations of triglycerides and 2-h glucose, and higher systolic blood pressure, as well as an increased risk…”
BackgroundMethodInfluentialSelf-citationAdiposity and asthma in adults: a bidirectional Mendelian randomisation analysis of The HUNT Study
Sun, Y., Brumpton, B. M., Langhammer, A., Chen, Y., Kvaløy, K., & Mai, X. (2019) · Thorax · doi:10.1136/thoraxjnl-2019-213678 · Cited by 40
The LCORL Locus Is under Selection in Large-Sized Pakistani Goat Breeds
Saif, R., Henkel, J., Jagannathan, V., Drögemüller, C., Flury, C., & Leeb, T. (2020) · Genes · doi:10.3390/genes11020168 · Cited by 41
“Examples include the WARS2 gene, which is under selection in BAR, BEE, DDP, KAM, and NAC and associated with body fat distribution in humans [39], or ADAMTS6, which is under selection in BEE, DDP, KAM, and NAC and associated with bone length in mice [40].”
BackgroundYang, S., & Zhou, X. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac039 · Cited by 39
“With these criteria, we obtained 25 datasets for 19 quantitative traits that include SH (n = 253 288) [57], BMD (n = 66 628) [58], HDL_GLGC (n = 188 577) [59], HDL_meta (n = 19 840) [60], HDL_NMR (n = 24 925) [61], PLT (n = 4250) [62], BMI (n = 253 288) [63], AM_RG1 (n = 49 427) [64], AM_RG2 (n = 329 345) [65], HC (n…”
LGR4: A New Receptor Member in Endocrine and Metabolic Diseases
Zhang, N., Yuan, M., & Wang, J. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad003 · Cited by 43
Multivariable MR Can Mitigate Bias in Two‐Sample MR Using Covariable‐Adjusted Summary Associations
Gilbody, J., Borges, M. C., Smith, G. D., & Sanderson, E. C. M. (2025) · Genetic Epidemiology · doi:10.1002/gepi.22606 · Cited by 34
“To estimate the effect of WC on SBP we used GWAS summary data for WC from a GIANT study, this data was available both unadjusted and adjusted for BMI (Shungin et al. 2015).”
CNV analysis and mutation screening indicate an important role for the NPY4R gene in human obesity
Aerts, E., Beckers, S., Zegers, D., Hoorenbeeck, K. V., Massa, G., Verrijken, A., Verhulst, S. L., Gaal, L. F. V., & Hul, W. V. (2016) · Obesity · doi:10.1002/oby.21435 · Cited by 39
“Given the estimated heritability, extensive genome-wide association studies (GWASs) have been performed to identify common single-nucleotide polymorphisms (SNPs) underlying the heritable risk for human obesity (4,5).”
BackgroundMijajlovic, M. D., Aleksić, V., Šternić, N., Mirkovic, M., & Bornstein, N. M. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s128807 · Cited by 39
“However, the woman is at risk of developing prediabetes or even DM. 18,23 Age The prevalence of DM and prediabetes is increasing with age.”
InfluentialEpigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
Kvaløy, K., Page, C. M., & Holmen, T. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-34003-8 · Cited by 39
Ólafsdóttir, Þ., Þorleifsson, G., Sulem, P., Stefánsson, Ó. A., Medek, H., Olafsson, K., Ingthorsson, O., Gudmundsson, V., Jónsdóttir, I., Halldorsson, G. H., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-0857-9 · Cited by 39
Genetic Influences on Disease Subtypes
Dahl, A. W., & Zaitlen, N. (2020) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120319-095026 · Cited by 36
Metabolic signals in sleep regulation: recent insights
Basheer, R., & Shukla, C. (2016) · Nature and Science of Sleep · doi:10.2147/nss.s62365 · Cited by 44
“Another promising evidence has emerged from the epidemiological studies using genome-wide associations revealing close linkage between sleep/circadian and metabolism-related genes.(11,12) Thus, the circadian rhythmicity, sleep-wake, and feeding behavior are integral to bodily energy homeostasis.”
Mahajan, A., Taliun, D., Thurner, M., Robertson, N. R., Torres, J., Rayner, N. W., Steinthórsdóttir, V., Scott, R. A., Grarup, N., Cook, J. P., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/245506 · Cited by 37
Self-citationSaadh, M. J., Pal, R. S., Arias‐Gonzáles, J. L., Gavilán, J. C. O., Darshan, J. C., Mohany, M., Al-Rejaie, S. S., Bahrami, A., Kadham, M. J., Amin, A. H., et al. (2023) · Nutrients · doi:10.3390/nu15051202 · Cited by 36
“GWAS summary statistics for waist circumference, waist-to-hip ratio, and hip circumference were obtained from GIANT (Genetic Investigation of Anthropometric Traits) [21].”
MethodRetracted
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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- 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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- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
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- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
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- 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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