Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans
Open accessPublished version of a preprint
Abstract
Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15 , potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p FDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Only SNP-based cis associations with GDF-15 itself have been identified in previous pQTL studies.
“only SNP-based cis associations with GDF-15 itself have been identified in previous pQTL studies9,86.”
From Genetic determinants of plasma protein levels in the Estonian population (2024) · cites this paper as [86]
The Results section (GWAS of plasma GDF15 levels; page unavailable) identifies SNP associations at the GDF15 locus, and the conditioned meta-analysis reports that only signals within 1 Mb of the gene reached significance. These findings support cis associations in this paper, but its discussion of earlier studies does not establish that previous pQTL studies identified *only* cis associations. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPlatform-specific and platform-discordant PAVs may bias MR results if used as genetic instruments for circulating protein abundances, in some cases resulting in platform-specific and/or platform-discordant MR estimates.
“We show that platform-specific and platform-discordant PAVs may bias MR results if used as genetic instruments for circulating protein abundances35, in some cases resulting in platform-specific and/or platform-discordant MR estimates.”
From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [35]
Recent findings support GDF-15's role as a biomarker of metabolic stress.
“and recent findings support its role as a biomarker of metabolic stress86.”
From Genetic determinants of plasma protein levels in the Estonian population (2024) · cites this paper as [86]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Part of this paper’s reference list could not be split into single entries.
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Self-citationSudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728 · see citing works
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816 · see citing works
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018) · Nature Genetics · doi:10.1038/s41588-018-0099-7 · Cited by 8,591 · see citing works
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205 · see citing works
METAL: fast and efficient meta-analysis of genomewide association scans
Willer, C. J., Li, Y., & Abecasis, G. R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq340 · Cited by 5,205 · see citing works
Howie, B. N., Donnelly, P., & Marchini, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000529 · Cited by 3,928 · see citing works
European Guidelines for Obesity Management in Adults
Yumuk, V., Tsigos, C., Fried, M., Schindler, K., Busetto, L., Micic, D., & Toplak, H. (2015) · Obesity Facts · doi:10.1159/000442721 · Cited by 3,432 · see citing works
A new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609 · see citing works
Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis
Võsa, U., Claringbould, A., Westra, H.-J., Bonder, M. J., Deelen, P., Zeng, B., Kirsten, H., Saha, A., Kreuzhuber, R., Kasela, S., et al. (2018) · doi:10.1101/447367 · Cited by 2,607 · see citing works
Võsa, U., Claringbould, A., Westra, H.-J., Bonder, M. J., Deelen, P., Zeng, B., Kirsten, H., Saha, A., Kreuzhuber, R., Yazar, S., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00913-z · Cited by 2,607 · see citing works
Yengo, L., Sidorenko, J., Kemper, K. E., Zheng, Z., Wood, A. R., Weedon, M. N., Frayling, T. M., Hirschhorn, J. N., Yang, J., & Visscher, P. M. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy271 · Cited by 2,305 · see citing works
Genomic atlas of the human plasma proteome
Sun, B. B., Maranville, J. C., Peters, J. E., Stacey, D., Staley, J. R., Blackshaw, J., Burgess, S., Jiang, T., Paige, E., Surendran, P., et al. (2018) · Nature · doi:10.1038/s41586-018-0175-2 · Cited by 2,268 · see citing works
Self-citationGuidelines for performing Mendelian randomization investigations
Burgess, S., Smith, G. D., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., et al. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.1 · Cited by 1,816 · see citing works
Mahajan, A., Taliun, D., Thurner, M., Robertson, N. R., Torres, J. M., Rayner, N. W., Payne, A. J., Steinthorsdottir, V., Scott, R. A., Grarup, N., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0241-6 · Cited by 1,744 · see citing works
New genetic loci link adipose and insulin biology to body fat distribution
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., et al. (2015) · Nature · doi:10.1038/nature14132 · Cited by 1,580 · cited 1× · see citing works
“, 2018), WHR (n=485,486) (Shungin et al., 2015), 669 glucose (n=314,916) (Neale, 2018), type 2 diabetes (n cases=74,124, n controls=824,006) 670 (Mahajan et al.”
Guidelines for performing Mendelian randomization investigations
Burgess, S., Davey Smith, G., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., et al. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.2 · Cited by 1,273 · see citing works
The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease
Astle, W. J., Elding, H., Jiang, T., Allen, D., Ruklisa, D., Mann, A. L., Mead, D., Bouman, H., Riveros-Mckay, F., Kostadima, M. A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.042 · Cited by 1,224 · see citing works
Self-citationMIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily
Bootcov, M. R., Bauskin, A. R., Valenzuela, S. M., Moore, A. G., Bansal, M., He, X. Y., Zhang, H. P., Donnellan, M., Mahler, S. M., Pryor, K., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11514 · Cited by 1,180 · see citing works
FINEMAP: efficient variable selection using summary data from genome-wide association studies
Benner, C., Spencer, C. C. A., Havulinna, A. S., Salomaa, V., Ripatti, S., & Pirinen, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw018 · Cited by 815 · see citing works
Self-citationGFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates
Mullican, S. E., Lin-Schmidt, X., Chin, C.-N., Chavez, J. A., Furman, J. L., Armstrong, A. A., Beck, S. C., South, V. J., Dinh, T. Q., Cash-Mason, T. D., et al. (2017) · Nature Medicine · doi:10.1038/nm.4392 · Cited by 774 · see citing works
An atlas of genetic influences on osteoporosis in humans and mice
23andMe Research Team, Morris, J. A., Kemp, J. P., Youlten, S. E., Laurent, L., Logan, J. G., Chai, R. C., Vulpescu, N. A., Forgetta, V., Kleinman, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0302-x · Cited by 773 · see citing works
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals
Folkersen, L., Gustafsson, S., Wang, Q., Hansen, D. H., Hedman, Å. K., Schork, A., Page, K., Zhernakova, D. V., Wu, Y., Peters, J., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00287-2 · Cited by 705 · see citing works
Self-citationThe metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Emmerson, P. J., Wang, F., Du, Y., Liu, Q., Pickard, R. T., Gonciarz, M. D., Coskun, T., Hamang, M. J., Sindelar, D. K., Ballman, K. K., et al. (2017) · Nature Medicine · doi:10.1038/nm.4393 · Cited by 675 · see citing works
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand
Yang, L., Chang, C.-C., Sun, Z., Madsen, D., Zhu, H., Padkjær, S. B., Wu, X., Huang, T., Hultman, K., Paulsen, S. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4394 · Cited by 668 · see citing works
Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., Heineke, J., Kotlarz, D., Xu, J., Molkentin, J. D., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000202805.73038.48 · Cited by 651 · see citing works
Self-citationNon-Homeostatic Body Weight Regulation Through a Brainstem-Restricted Receptor for GDF15
Hsu, J.-Y., Crawley, S., Chen, M., Ayupova, D. A., Lindhout, D. A., Higbee, J., Kutach, A., Joo, W., Gao, Z., Fu, D., et al. (2017) · Nature · doi:10.1038/nature24042 · Cited by 616 · see citing works
Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1
Johnen, H., Lin, S., Kuffner, T., Brown, D. A., Tsai, V. W.-W., Bauskin, A. R., Wu, L., Pankhurst, G., Jiang, L., Junankar, S., et al. (2007) · Nature Medicine · doi:10.1038/nm1677 · Cited by 612 · see citing works
Rare variant contribution to human disease in 281,104 UK Biobank exomes
Wang, Q., Dhindsa, R. S., Carss, K., Harper, A. R., Nag, A., Tachmazidou, I., Vitsios, D., Deevi, S. V. V., Mackay, A., Muthas, D., et al. (2021) · Nature · doi:10.1038/s41586-021-03855-y · Cited by 604 · see citing works
Self-citationGDF15 mediates the effects of metformin on body weight and energy balance
Coll, A. P., Chen, M., Taskar, P., Rimmington, D., Patel, S., Tadross, J. A., Cimino, I., Yang, M., Welsh, P., Virtue, S., et al. (2020) · Nature · doi:10.1038/s41586-019-1911-y · Cited by 584 · see citing works
GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease
Wang, D., Day, E. A., Townsend, L. K., Djordjevic, D., Jørgensen, S. B., & Steinberg, G. R. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00529-7 · Cited by 526 · see citing works
GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans
Patel, S., Alvarez-Guaita, A., Melvin, A., Rimmington, D., Dattilo, A., Miedzybrodzka, E. L., Cimino, I., Maurin, A.-C., Roberts, G. P., Meek, C. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.016 · Cited by 509 · cited 5× · see citing works
“(Borner, Shaulson, et al., 2020; Patel et al., 2019), as well as vomiting in shrews, suncus murinus, 374”
BackgroundInfluentialAdela, R., & Banerjee, S. K. (2015) · Journal of Diabetes Research · doi:10.1155/2015/490842 · Cited by 474 · see citing works
Tsai, V. W.-W., Husaini, Y., Sainsbury, A., Brown, D. A., & Breit, S. N. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.018 · Cited by 414 · see citing works
Cardiovascular risk factor changes in Finland, 1972–1997
Vartiainen, E. A., Jousilahti, P., Alfthan, G., Sundvall, J., Pietinen, P., & Puska, P. (2000) · International Journal of Epidemiology · doi:10.1093/ije/29.1.49 · Cited by 401 · see citing works
Day, E. A., Ford, R. J., Smith, B. K., Mohammadi-Shemirani, P., Morrow, M. R., Gutgesell, R. M., Lu, R., Raphenya, A. R., Kabiri, M., McArthur, A. G., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0146-4 · Cited by 307 · see citing works
Cohort Profile: The National FINRISK Study
Borodulin, K., Tolonen, H. K., Jousilahti, P., Jula, A. M., Juolevi, A., Koskinen, S. V. P., Kuulasmaa, K., Laatikainen, T. K., Männistö, S., Peltonen, M., et al. (2017) · International Journal of Epidemiology · doi:10.1093/ije/dyx239 · Cited by 300 · see citing works
Self-citationMacrophage inhibitory cytokine‐1 (MIC‐1/GDF15): a new marker of all‐cause mortality
Wiklund, F. E., Bennet, A. M., Magnusson, P. K. E., Eriksson, U. K., Lindmark, F., Wu, L., Yaghoutyfam, N., Marquis, C. P., Stattin, P. E., Pedersen, N. L., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00629.x · Cited by 290 · see citing works
Kempf, T., Horn-Wichmann, R., Brabant, G. E., Peter, T., Allhoff, T., Klein, G. G., Drexler, H., Johnston, N., Wallentin, L. C., & Wollert, K. C. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2006.076828 · Cited by 286 · see citing works
Self-citationAkbari, P., Gilani, A., Sosina, O., Kosmicki, J. A., Khrimian, L., Fang, Y.-Y., Persaud, T., Garcia, V., Sun, D., Li, A., et al. (2021) · Science · doi:10.1126/science.abf8683 · Cited by 276 · see citing works
Self-citationBrown, D. A., Breit, S. N., Buring, J. E., Fairlie, W. D., Bauskin, A. R., Liu, T., & Ridker, P. M. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09093-1 · Cited by 258 · see citing works
GDF15: a hormone conveying somatic distress to the brain
Lockhart, S. M., Saudek, V., & O’Rahilly, S. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa007 · Cited by 256 · see citing works
GDF15 induces anorexia through nausea and emesis
Borner, T., Shaulson, E. D., Ghidewon, M. Y., Barnett, A. B., Horn, C. C., Doyle, R. P., Grill, H. J., Hayes, M. R., & De Jonghe, B. C. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.12.004 · Cited by 255 · see citing works
Daniels, L. B., Clopton, P., Laughlin, G. A., Maisel, A. S., & Barrett-Connor, E. L. (2011) · Circulation · doi:10.1161/circulationaha.110.979740 · Cited by 248 · see citing works
Lind, L., Wallentin, L. C., Kempf, T., Tapken, H., Quint, A., Lindahl, B., Olofsson, S., Venge, P., Larsson, A. O., Hulthe, J., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp261 · Cited by 244 · see citing works
Self-citationHepatocyte growth factor/ MET in cancer progression and biomarker discovery
Matsumoto, K., Umitsu, M., Silva, D. M. D., Roy, A., & Bottaro, D. P. (2017) · Cancer Science · doi:10.1111/cas.13156 · Cited by 238 · see citing works
Who’s Who? Detecting and Resolving Sample Anomalies in Human DNA Sequencing Studies with Peddy
Pedersen, B. S., & Quinlan, A. R. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.01.017 · Cited by 237 · see citing works
Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys
Xiong, Y., Walker, K., Min, X., Hale, C., Tran, T., Komorowski, R., Yang, J., Davda, J., Nuanmanee, N., Kemp, D., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aan8732 · Cited by 236 · see citing works
Wollert, K. C., Kempf, T., Lagerqvist, B., Lindahl, B., Olofsson, S., Allhoff, T., Peter, T., Siegbahn, A., Venge, P., Drexler, H., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.697714 · Cited by 231 · see citing works
Self-citationGrowth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction
Khan, S., Ng, K., Dhillon, O. S., Kelly, D., Quinn, P., Squire, I. B., Davies, J. E., & Ng, L. L. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehn600 · Cited by 218 · see citing works
Holmes, M. V., Lange, L. A., Palmer, T., Lanktree, M. B., North, K. E., Almoguera, B., Buxbaum, S., Chandrupatla, H. R., Elbers, C. C., Guo, Y., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.12.014 · Cited by 216 · see citing works
Association of C-Reactive Protein With Blood Pressure and Hypertension
Smith, G. D., Lawlor, D. A., Harbord, R. M., Timpson, N. J., Rumley, A., Lowe, G. D. O., Day, I. N. M., & Ebrahim, S. B. J. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000160351.95181.d0 · Cited by 210 · see citing works
Zimmers, T. A., Jin, X., Hsiao, E. C., McGrath, S. A., Esquela, A. F., & Koniaris, L. G. (2005) · PubMed · Cited by 199 · see citing works
Growth Differentiation Factor–15 and Risk of CKD Progression
Nair, V., Robinson‐Cohen, C., Smith, M. R., Bellovich, K. A., Bhat, Z. Y., Bobadilla, M., Brosius, F. C., de Boer, I. H., Essioux, L., Formentini, I., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016080919 · Cited by 192 · see citing works
Vila, G., Riedl, M., Anderwald, C. H., Resl, M., Handisurya, A., Clodi, M., Prager, G., Ludvik, B. H., Krebs, M., & Luger, A. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2010.153726 · Cited by 185 · see citing works
Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum
Fejzo, M. S., Sazonova, O. V., Sathirapongsasuti, J. F., Hallgrímsdóttir, I. B., Vacic, V., MacGibbon, K., Schoenberg, F. P., Mancuso, N., Slamon, D. J., Mullin, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03258-0 · Cited by 184 · see citing works
Moore, A. G., Brown, D. A., Fairlie, W. D., Bauskin, A. R., Brown, P. K., Munier, M. L. C., Russell, P. K., Salamonsen, L. A., Wallace, E. M., & Breit, S. N. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7007 · Cited by 181 · see citing works
Rohatgi, A. K., Patel, P. C., Das, S. R., Ayers, C. R., Khera, A., Martinez‐Rumayor, A., Berry, J. D., McGuire, D. K., & de Lemos, J. A. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.171926 · Cited by 179 · see citing works
Growth Differentiation Factor 15 as a Novel Biomarker for Metformin
Gerstein, H. C., Pare, G., Hess, S., Ford, R. J., Sjaarda, J., Raman, K., McQueen, M., Lee, S., Haenel, H., & Steinberg, G. R. (2017) · Diabetes Care · doi:10.2337/dc16-1682 · Cited by 169 · see citing works
Emmerson, P. J., Duffin, K. L., Chintharlapalli, S. R., & Wu, X. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01712 · Cited by 168 · see citing works
Bonaca, M. P., Morrow, D. A., D, E. B. M., Cannon, C. P., Jiang, S., Breher, S., Sabatine, M. S., Kempf, T., Wallentin, L. C., & Wollert, K. C. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.213512 · Cited by 167 · see citing works
Self-citationMoore, C. S., Sambrook, J., Walker, M. R., Tolkien, Z., Kaptoge, S. K., Allen, D., Mehenny, S., Mant, J., Angelantonio, E. D., Thompson, S. G., et al. (2014) · Trials · doi:10.1186/1745-6215-15-363 · Cited by 145 · see citing works
Genetic architecture of host proteins involved in SARS-CoV-2 infection
Pietzner, M., Wheeler, E., Carrasco-Zanini, J., Raffler, J., Kerrison, N. D., Oerton, E., Auyeung, V. P. W., Luan, J., Finan, C., Casas, J. P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19996-z · Cited by 145 · see citing works
Clinical and Genetic Correlates of Growth Differentiation Factor 15 in the Community
Ho, J. E., Mahajan, A., Chen, M., Larson, M. G., McCabe, E. L., Ghorbani, A., Cheng, S. C., Johnson, A. D., Lindgren, C. M., Kempf, T., et al. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2012.190322 · Cited by 133 · see citing works
Self-citationGDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss
Borner, T., Wald, H. S., Ghidewon, M. Y., Zhang, B., Wu, Z., Jonghe, B. C. D., Breen, D. M., & Grill, H. J. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107543 · Cited by 102 · see citing works
Brown, D. A., Moore, J. J., Johnen, H., Smeets, T. J. M., Bauskin, A. R., Kuffner, T., Weedon, H., Milliken, S. T., Tak, P. P., Smith, M., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22410 · Cited by 99 · see citing works
Tsai, V. W.-W., Macia, L., Feinle‐Bisset, C., Manandhar, R., Astrup, A. V., Raben, A., Lorenzen, J. K., Schmidt, P. T., Wiklund, F. E., Pedersen, N. L., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133362 · Cited by 94 · see citing works
GDF15 deficiency promotes high fat diet-induced obesity in mice
Tran, T., Yang, J. O., Gardner, J., & Xiong, Y. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201584 · Cited by 94 · see citing works
Radioimmunoassay for the detection of leptin in human serum
Horn, R., Geldszus, R., Pötter, E., Mühlen, A. V. Z., & Brabant, G. E. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211484 · Cited by 69 · see citing works
Endocrine and Metabolic Complications After Bariatric Surgery
Jammah, A. A. (2015) · Saudi Journal of Gastroenterology · doi:10.4103/1319-3767.164183 · Cited by 65 · see citing works
The Incremental Prognostic and Clinical Value of Multiple Novel Biomarkers in Heart Failure
Jackson, C. E., Haig, C. E., Welsh, P. I., Dalzell, J. R., Tsorlalis, I. K., McConnachie, A., Preiss, D., Anker, S. D., Sattar, N. A., Petrie, M. C., et al. (2016) · European Journal of Heart Failure · doi:10.1002/ejhf.543 · Cited by 63 · see citing works
Novel biomarkers in acute heart failure: MR-pro-adrenomedullin
Peacock, W. F. (2014) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2014-0222 · Cited by 58 · see citing works
Moore, A. G. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.12.4781 · Cited by 55 · see citing works
Madonna, R., Çevik, C., Nasser, M., & Caterina, R. D. (2012) · Thrombosis and Haemostasis · doi:10.1160/th11-10-0711 · Cited by 54 · see citing works
Use of BNP and CRP as Biomarkers in Assessing Cardiovascular Disease:Diagnosis Versus Risk
Miller, V. M., Redfield, M. M., & McConnell, J. P. (2006) · Current Vascular Pharmacology · doi:10.2174/157016107779317251 · Cited by 53 · see citing works
Yeung, S. L. A., Luo, S., & Schooling, C. M. (2019) · Diabetologia · doi:10.1007/s00125-019-4913-2 · Cited by 53 · see citing works
An Automated Assay for Growth Differentiation Factor 15
Wollert, K. C., Kempf, T., Giannitsis, E., Bertsch, T., Braun, S., Maier, H., Reim, M., & Christenson, R. H. (2017) · The Journal of Applied Laboratory Medicine · doi:10.1373/jalm.2016.022376 · Cited by 49 · see citing works
Self-citationCheung, C., Tan, K. C. B., Au, P. C.-M., Li, G. H., & Cheung, B. M. Y. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.02.021 · Cited by 48 · see citing works
Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
Fejzo, M. S., Arzy, D., Tian, R., MacGibbon, K., & Mullin, P. (2018) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-0661-0287 · Cited by 46 · see citing works
GDF15—From Biomarker to Allostatic Hormone
O’Rahilly, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.017 · Cited by 43 · see citing works
Jiang, J., Thalamuthu, A., Ho, J. E., Mahajan, A., Ek, W. E., Brown, D. A., Breit, S. N., Wang, T. J., Gyllensten, U. B., Chen, M., et al. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00097 · Cited by 42 · see citing works
Fairlie, W. D., Russell, P. K., Wu, W. M., Moore, A. G., Zhang, H., Brown, P. K., Bauskin, A. R., & Breit, S. N. (2000) · Biochemistry · doi:10.1021/bi001064p · Cited by 34 · see citing works
Metabolic and nutritional complications of bariatric surgery : a review.
Mesureur, L., & Arvanitakis, M. (2017) · PubMed · Cited by 18 · see citing works
GDF15 tells the brain to lose weight
Villanueva, M. T. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.241 · Cited by 16 · see citing works
Sinning, C., Ojeda, F., Wild, P. S., Schnabel, R. B., Schwarzl, M., Ohdah, S., Lackner, K. J., Pfeiffer, N., Michal, M., Blettner, M., et al. (2016) · Clinical Research in Cardiology · doi:10.1007/s00392-016-1066-x · Cited by 14 · see citing works
Self-citationGenetic architecture of host proteins interacting with SARS-CoV-2Preprint
Pietzner, M., Wheeler, E., Carrasco-Zanini, J., Raffler, J., Kerrison, N. D., Oerton, E., Auyeung, V. P. W., Luan, J., Finan, C., Casas, J. P., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.01.182709 · Cited by 12 · see citing works
Genetically proxied growth‐differentiation factor 15 levels and body mass index
Karhunen, V., Larsson, S. C., & Gill, D. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14808 · Cited by 9 · see citing works
Vilarrasa, N., Radilla-Vázquez, R. B., Parra-Rojas, I., Nozaki, T., Furukawa, T., Tanahashi, T., Morita, C., Hata, T., Komaki, G., Sudo, N., et al. (2016) · Obesity Facts · doi:10.1159/000444869 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Li, X., Huai, Q., Zhu, C., Zhang, X., Xu, W., Dai, H., & Wang, H. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.07.009 · Cited by 80 · see citing works
Overview of growth differentiation factor 15 in metabolic syndrome
Asrih, M., Wei, S., Nguyen, T. T., Yi, H., Ryu, D., & Gariani, K. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17725 · Cited by 70 · see citing works
Common pitfalls in drug target Mendelian randomization and how to avoid them
Gill, D., Dib, M., Cronjé, H. T., Karhunen, V., Woolf, B. A. R., Gagnon, É., Daghlas, I., Nyberg, M., Drakeman, D. L., & Burgess, S. (2024) · BMC Medicine · doi:10.1186/s12916-024-03700-9 · Cited by 49 · see citing works
Schwarz, A., Kinscherf, R., & Bonaterra, G. A. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2403081 · Cited by 49 · see citing works
Blood protein levels predict leading incident diseases and mortality in UK BiobankPreprint
Gadd, D. A., Hillary, R. F., Kuncheva, Z., Mangelis, T., Cheng, Y., Dissanayake, M., Admanit, R., Gagnon, J., Lin, T.-C., Ferber, K. L., et al. (2023) · medRxiv · doi:10.1101/2023.05.01.23288879 · Cited by 31 · see citing works
Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans
Chrysafi, P., Valenzuela‐Vallejo, L., Stefanakis, K., Kelesidis, T., Connelly, M. A., & Mantzoros, C. S. (2024) · Nature Communications · doi:10.1038/s41467-024-49366-y · Cited by 17 · see citing works
Mazidi, M., Wright, N., Yao, P., Kartsonaki, C., Millwood, I. Y., Fry, H., Said, S., Pozarickij, A., Pei, P., Chen, Y., et al. (2024) · European Journal of Epidemiology · doi:10.1007/s10654-024-01168-8 · Cited by 16 · see citing works
Nopp, S., Moik, F., Kraler, S. C., Englisch, C., Preusser, M., von Eckardstein, A., Pabinger, I., Lüscher, T. F., & Ay, C. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2023.04.043 · Cited by 15 · see citing works
Cross-ancestry comparison of aptamer and antibody protein measures
Nicholas, J. C., Katz, D. H., Tahir, U. A., Debban, C. L., Aguet, F., Blackwell, T., Bowler, R. P., Broadaway, K. A., Chen, J., Clish, C. B., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-67814-1 · Cited by 13 · see citing works
Genetic determinants of plasma protein levels in the Estonian population
Kalnapenkis, A., Jõeloo, M., Lepik, K., Kukuškina, V., Kals, M., Alasoo, K., Estonian Biobank Research Team, Metspalu, A., Milani, L., Nelis, M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-57966-3 · Cited by 11 · see citing works
Damanti, S., Sciorati, C., LORENZO, R. D., Avola, A., Ruggiero, M. P., Santoro, S., Senini, E., Messina, M., Farina, F., Festorazzi, C., et al. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112124 · Cited by 11 · see citing works
HFpEF: New biomarkers and their diagnostic and prognostic value
Shaik, S. P., Karan, H. H., Singh, A., Attuluri, S. K., Khan, A. A. N., Zahid, F., & Patil, D. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.102155 · Cited by 11 · see citing works
Lombardi, C., Marandola, M., Loria, V., Urbani, A., & Baroni, S. (2026) · Journal of Personalized Medicine · doi:10.3390/jpm16010016 · Cited by 10 · see citing works
Wang, J., Geng, T., Yao, X., & Liu, Y. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05265-4 · Cited by 8 · see citing works
Lu, L., Johnson, C. H., Khan, S. A., & Irwin, M. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.01.004 · Cited by 8 · see citing works
Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling
Blew, C., Duggan, M. R., Tsitsipatis, D., Gómez, G., Rodriguez-Hernandez, Z., Pilling, L. C., Chen, J., Jacobsen, E. M., Dark, H. E., Lu, Y., et al. (2026) · Science Advances · doi:10.1126/sciadv.aec7614 · Cited by 5 · see citing works
Revisiting the role of GDF15 in atherosclerosis in mouse and human
Liu, M., Liu, Z., Leng, R., Strijdom, H., Weng, J., & Xu, S. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01561-3 · Cited by 5 · see citing works
Billeson, K., Baldimtsi, E., Wahlberg, J., & Whiss, P. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137328 · Cited by 5 · see citing works
GDF15 and its receptors as pathways mediating smoking related weight change
Tinworth, A. C., Iona, A., Yao, P., Millwood, I. Y., Fry, H., Clarke, J., Wang, B., Mazidi, M., Kartsonaki, C., Walters, R. G., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105806 · Cited by 4 · see citing works
Isnard, S., Royston, L., Berini, C. A., Mabanga, T., Al‐Abdulmalek, A., Aiyana, O., Sun, L., Far, M. E., Pagliuzza, A., Planas, D., et al. (2026) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiag202 · Cited by 3 · see citing works
Pereira, D. A., Kaihara, J. N. S., Passeti, L. F. P., de Araújo, J. L. F., Souza, R. P., Palei, A. C., Cavalli, R. C., Deng, C., Ahituv, N., Sandrim, V. C., et al. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11629-w · Cited by 2 · see citing works
Ker, C.-R., Chen, Y.-L., Feng, C., Wang, S.-H., Lee, C., & Chan, T. (2026) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2025.04.027 · Cited by 1 · see citing works
Wu, C., Wang, T., Gong, S., Zhang, J., Mann, C. G., Li, M., Liu, Z., Sun, Y., Shi, S., 刘政宏, et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117603 · Cited by 1 · see citing works
Wang, R., Tan, H., Li, Z., Li, D., Pan, Y., & He, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1902574 · Cited by 1 · see citing works
Growth Differentiation Factor 15 Connects Stress and Ageing in a UK Biobank CohortPreprint
Lehrer, S. P., & Rheinstein, P. H. (2025) · medRxiv · doi:10.1101/2025.07.04.25330886
Merits and challenges of plasma proteomics on association replicabilityPreprint
Jiao, Z., Zhang, Y., Lai, Y., Kang, J., Ma, L., Zhao, W., You, J., Cheng, W., & Feng, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.01.673490
Pukhalskaya, A. E., Медведев, Д. С., Полякова, В. О., Voloshin, S. V., Kozlov, K. L., & Alekseev, S. M. (2026) · Успехи геронтологии · doi:10.34922/ae.2026.39.3.020
Bonaventura, I., Weigand, I., Isidori, A. M., Kroiß, M., & Reincke, M. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnag035
- Authors
- Lemmelä, S., Wigmore, E. M., Benner, C., Havulinna, A. S., Ong, R. M., Kempf, T., Wollert, K. C., Blankenberg, S., Zeller, T., Peters, J. E., Salomaa, V., Fritsch, M., March, R., Palotie, A., Daly, M., Butterworth, A. S., Kinnunen, M., Paul, D. S., & Matakidou, A.
- Affiliations
- University of Helsinki (FI)
- AstraZeneca (United Kingdom) (GB)
- University of Cambridge (GB)
- Medizinische Hochschule Hannover (DE)
- Universität Hamburg (DE)
- Finnish Institute for Health and Welfare (FI)
- AstraZeneca (Sweden) (SE)
- Broad Institute (US)
- Institute for Molecular Medicine Finland, University of Helsinki
- Corresponding author
- Wigmore, Eleanor M
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-08-02
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9391041
- OpenAlex
- W4289522605
- Cited by
- 28
- References
- 88
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 5 · 2023: 6
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Työväentutkimus Vuosikirja (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Apollo
- Apollo (cc-by)
- Funders
- NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)
- Sydäntutkimussäätiö
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- growth differentiation factor 15, GDF15, cardiometabolic disease, missense mutations, HDL cholesterol, body mass index, all-cause mortality, respiratory diseases, mental illness, inflammatory markers, causal inference, genetic fine-mapping
- MeSH terms
- Cardiovascular Diseases, Humans, Biomarkers, Body Mass Index, Genome-Wide Association Study, Mendelian Randomization Analysis
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
