From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus
Open accessAbstract
Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.
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Transcriptomics, employing either expression arrays or RNA-Seq, has proven to be particularly useful for identifying causal genes at GWAS loci.
“Thus, transcriptomics, employing either expression arrays or RNA-Seq (Box 1), has proven to be particularly useful for identifying causal genes at GWAS loci [16, 22–24].”
From Multi-omics approaches to disease (2017) · cites this paper as [24]
One early success described how regulatory variants that modulate SORT1 expression influence low-density lipoprotein cholesterol and myocardial infarction risk.
“One early success described how regulatory variants that modulate SORT1 expression influence low-density lipoprotein cholesterol and myocardial infarction risk101”
From A brief history of human disease genetics (2020) · cites this paper as [101]
In some cases, associations between common variants and endophenotypes have been confirmed by in vitro biochemical assays for structural and regulatory effects.
“in some cases these have been confirmed by in vitro biochemical assays for structural and regulatory effects [eg83–85].”
From Rare and common variants: twenty arguments (2012) · cites this paper as [83]
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Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487 · see citing works
Self-citationTherapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
Soutschek, J., Akinc, A., Bramlage, B., Charissé, K., Constien, R., Donoghue, M., Elbashir, S. M., Geick, A., Hadwiger, P., Harborth, J., et al. (2004) · Nature · doi:10.1038/nature03121 · Cited by 2,189 · see citing works
Self-citationGenomewide Association Analysis of Coronary Artery Disease
Samani, N. J., Erdmann, J., Hall, A. S., Hengstenberg, C., Mangino, M., Mayer, B., Dixon, R. J., Meitinger, T., Braund, P., Wichmann, H.-E., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072366 · Cited by 2,044 · see citing works
Newly identified loci that influence lipid concentrations and risk of coronary artery disease
Willer, C. J., Sanna, S., Jackson, A. U., Scuteri, A., Bonnycastle, L. L., Clarke, R., Heath, S. C., Timpson, N. J., Najjar, S. S., Stringham, H. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.76 · Cited by 1,585 · see citing works
Kathiresan, S., Melander, O., Guiducci, C., Surti, A., Burtt, N. P., Rieder, M. J., Cooper, G. M., Roos, C., Voight, B. F., Havulinna, A. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.75 · Cited by 1,386 · see citing works
Self-citationCommon variants at 30 loci contribute to polygenic dyslipidemia
Kathiresan, S., Willer, C. J., Peloso, G. M., Demissie, S., Musunuru, K., Schadt, E. E., Kaplan, L., Bennett, D., Li, Y., Tanaka, T., et al. (2009) · Nature Genetics · doi:10.1038/ng.291 · Cited by 1,364 · see citing works
Self-citationHighly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
Si-Tayeb, K., Noto, F. K., Nagaoka, M., Li, J., Battle, M. A., Duris, C., North, P. E., Dalton, S., & Duncan, S. A. (2010) · Hepatology · doi:10.1002/hep.23354 · Cited by 1,282 · see citing works
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M. S., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S., Nguyen, D. N., Fuller, J. E., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,228 · see citing works
Self-citationMyocardial Infarction Genetics Consortium (2009) · Nature Genetics · doi:10.1038/ng.327 · Cited by 1,088 · see citing works
Sortilin is essential for proNGF-induced neuronal cell death
Nykjaer, A., Lee, R., Teng, K. K., Jansen, P., Madsen, P., Nielsen, M. S., Jacobsen, C., Kliemannel, M., Schwarz, E., Willnow, T. E., et al. (2004) · Nature · doi:10.1038/nature02319 · Cited by 962 · see citing works
Mapping the Genetic Architecture of Gene Expression in Human Liver
Schadt, E. E., Molony, C. M., Chudin, E., Hao, K., Yang, X., Lum, P. Y., Kasarskis, A., Zhang, B., Wang, S. S.-M., Suver, C., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060107 · Cited by 909 · see citing works
Self-citationMetabolic origins and clinical significance of LDL heterogeneity
Berneis, K. K., & Krauss, R. M. (2002) · Journal of Lipid Research · doi:10.1194/jlr.r200004-jlr200 · Cited by 896 · see citing works
Self-citationLoci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Aulchenko, Y. S., Janssens, A. C. J. W., Albert Hofman, D., Isaacs, A. J., Sijbrands, E. J. G., Witteman, J. C. M., van Duijn, C. M., Ripatti, S., Lindqvist, I., Perola, M., et al. (2008) · Nature Genetics · doi:10.1038/ng.269 · Cited by 846 · see citing works
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
Sabatti, C., Service, S. K., Hartikainen, A., Pouta, A. M., Ripatti, S., Brodsky, J. F., Jones, C. G., Zaitlen, N., Varilo, T., Kaakinen, M., et al. (2008) · Nature Genetics · doi:10.1038/ng.271 · Cited by 721 · see citing works
Frank-Kamenetsky, M. D., Grefhorst, A., Anderson, N. N., Racie, T., Bramlage, B., Akinc, A., Butler, D., Charissé, K., Dorkin, J. R., Fan, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805434105 · Cited by 635 · see citing works
Self-citationMonogenic hypercholesterolemia: new insights in pathogenesis and treatment
Rader, D. J., Cohen, J. C., & Hobbs, H. H. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18925 · Cited by 555 · see citing works
Self-citationAhn, S., Olive, M., Aggarwal, S., Krylov, D. Y., Ginty, D. D., & Vinson, C. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.967 · Cited by 502 · see citing works
Monogenic hypercholesterolemia: new insights in pathogenesis and treatment
Rader, D. J., Cohen, J. C., & Hobbs, H. H. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318925 · Cited by 468 · see citing works
Self-citationNielsen, M. S., Madsen, P., Christensen, E. I., Nykjær, A., Gliemann, J., Kasper, D., Pohlmann, R., & Petersen, C. M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.9.2180 · Cited by 438 · see citing works
Wallace, C., Newhouse, S., Braund, P. S., Zhang, F., Tobin, M. D., Falchi, M., Ahmadi, K. R., Dobson, R., Marçano, A. C. B., Hajat, C., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.11.001 · Cited by 437 · see citing works
Petersen, C. M., Nielsen, M. S., Nykjær, A., Jacobsen, L., Tommerup, N., Rasmussen, H. H., Røigaard-Petersen, H., Gliemann, J., Madsen, P., & Moestrup, S. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3599 · Cited by 417 · see citing works
Lipid Treatment Assessment Project 2
Waters, D. D., Brotons, C., Chiang, C.-W., Ferrières, J., Foody, J. M., Jukema, J. W., Santos, R. D., Verdejo, J., Messig, M., McPherson, R., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.838466 · Cited by 305 · see citing works
DNA Binding Specificity of the CCAAT/Enhancer-binding Protein Transcription Factor Family
Osada, S., Yamamoto, H., Nishihara, T., & Imagawa, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3891 · Cited by 295 · see citing works
Shi, J., & Kandror, K. V. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.04.004 · Cited by 203 · see citing works
Reiner, A. P., Barber, M., Guan, Y., Ridker, P. M., Lange, L. A., Chasman, D. I., Walston, J. D., Cooper, G. M., Jenny, N. S., Rieder, M. J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.03.017 · Cited by 186 · see citing works
Self-citationMusunuru, K., Orho-Melander, M., Caulfield, M. P., Li, S., Salameh, W. A., Reitz, R. E., Berglund, G., Hedblad, B., Engström, G., Williams, P. T., et al. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.109.190405 · Cited by 168 · see citing works
Self-citationHeart Attacks: Gone with the Century?
Brown, M. S., & Goldstein, J. L. (1996) · Science · doi:10.1126/science.272.5262.629 · Cited by 163 · see citing works
Linsel‐Nitschke, P., Heeren, J., Aherrahrou, Z., Bruse, P., Gieger, C., Illig, T., Prokisch, H., Heim, K., Doering, A., Peters, A., et al. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.06.034 · Cited by 157 · see citing works
Tanigawa, H., Billheimer, J. T., Tohyama, J., Zhang, Y., Rothblat, G. H., & Rader, D. J. (2007) · Circulation · doi:10.1161/circulationaha.107.704254 · Cited by 149 · see citing works
Self-citationCandidate Gene Association Resource (CARe)
Musunuru, K., Lettre, G., Young, T., Farlow, D., Pirruccello, J. P., Ejebe, K. G., Keating, B. J., Yang, Q., Chen, M., Lapchyk, N., et al. (2010) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.882696 · Cited by 139 · see citing works
Self-citationMiller, M., Shuman, J. D., Sebastian, T. B., Dauter, Z., & Johnson, P. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300417200 · Cited by 136 · see citing works
C/EBPα: a critical regulator of genes governing integrative metabolic processes
Darlington, G., Wang, N., & Hanson, R. W. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80024-7 · Cited by 124 · see citing works
Keebler, M., Sanders, C., Surti, A., Guiducci, C., Burtt, N. P., & Kathiresan, S. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.108.829473 · Cited by 62 · see citing works
Self-citationOlive, M., Williams, S. C., Dezan, C., Johnson, P., & Vinson, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.2040 · Cited by 60 · see citing works
Zeng, J., Racicott, J., & Morales, C. R. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.08.016 · Cited by 56 · see citing works
Self-citationKitajima, K., Marchadier, D. H. L., Miller, G. C., Gao, G.-P., Wilson, J. M., & Rader, D. J. (2006) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000231520.26490.54 · Cited by 54 · see citing works
Self-citationReversal of Small, Dense LDL Subclass Phenotype by Normalization of Adiposity
Siri‐Tarino, P. W., Williams, P. T., Fernstrom, H. A., Rawlings, R. S., & Krauss, R. M. (2009) · Obesity · doi:10.1038/oby.2009.146 · Cited by 42 · see citing works
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Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · see citing works
A general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183 · see citing works
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716 · see citing works
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487 · see citing works
Self-citationWiller (2013) · doi:10.1038/ng.2797 · Cited by 2,983 · see citing works
Multi-omics approaches to disease
Hasin, Y., Seldin, M., & Lusis, A. (2017) · Genome Biology · doi:10.1186/s13059-017-1215-1 · Cited by 2,953 · see citing works
Integrative approaches for large-scale transcriptome-wide association studies
Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B. W. J. H., Jansen, R., de Geus, E. J. C., Boomsma, D. I., Wright, F. A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3506 · Cited by 2,479 · see citing works
Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
Cardiogenics, Schunkert, H., the CARDIoGRAM Consortium, König, I. R., Kathiresan, S., Reilly, M. P., Assimes, T. L., Holm, H., Preuss, M., Stewart, A. F. R., et al. (2011) · Nature Genetics · doi:10.1038/ng.784 · Cited by 1,866 · see citing works
Self-citationGenome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849 · see citing works
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
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Gibson, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3118 · Cited by 1,278 · see citing works
Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations
Fulco, C. P., Nasser, J., Jones, T. R., Munson, G., Bergman, D. T., Subramanian, V., Grossman, S. R., Anyoha, R., Doughty, B. R., Patwardhan, T. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0538-0 · Cited by 1,111 · see citing works
van der Harst, P., & Verweij, N. (2018) · Circulation Research · doi:10.1161/circresaha.117.312086 · Cited by 1,141 · see citing works
The role of regulatory variation in complex traits and disease
Albert, F. W., & Kruglyak, L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3891 · Cited by 1,047 · see citing works
Initial impact of the sequencing of the human genome
Lander, E. S. (2011) · Nature · doi:10.1038/nature09792 · Cited by 1,044 · see citing works
The Post-GWAS Era: From Association to Function
Gallagher, M. D., & Chen-Plotkin, A. S. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.04.002 · Cited by 822 · see citing works
Beyond GWASs: Illuminating the Dark Road from Association to Function
Edwards, S. L., Beesley, J., French, J. D., & Dunning, A. M. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.10.012 · Cited by 784 · see citing works
Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787 · see citing works
A brief history of human disease genetics
Claussnitzer, M., Cho, J. H., Collins, R., Cox, N. J., Dermitzakis, E. T., Hurles, M. E., Kathiresan, S., Kenny, E. E., Lindgren, C. M., MacArthur, D. G., et al. (2020) · Nature · doi:10.1038/s41586-019-1879-7 · Cited by 697 · see citing works
Self-citationParker, S. C. J., Stitzel, M. L., Taylor, D. L., Orozco, J. M., Erdos, M. R., Akiyama, J. A., van Bueren, K. L., Chines, P. S., Narisu, N., Program, N. C. S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317023110 · Cited by 665 · see citing works
Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits
Wu, Y., Zeng, J., Zhang, F., Zhu, Z., Qi, T., Zheng, Z., Lloyd-Jones, L. R., Marioni, R. E., Martin, N. G., Montgomery, G. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03371-0 · Cited by 685 · see citing works
Chromatin marks identify critical cell types for fine mapping complex trait variants
Trynka, G., Sandor, C., Han, B., Xu, H., Stranger, B. E., Liu, X. S., & Raychaudhuri, S. (2013) · Nature Genetics · doi:10.1038/ng.2504 · Cited by 580 · see citing works
Systems genetics approaches to understand complex traits
Civelek, M., & Lusis, A. J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3575 · Cited by 621 · see citing works
Genetics of coronary artery disease: discovery, biology and clinical translation
Khera, A. V., & Kathiresan, S. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2016.160 · Cited by 659 · see citing works
Self-citationTewhey, R., Kotliar, D., Park, D. S., Liu, B., Winnicki, S., Reilly, S. K., Andersen, K. G., Mikkelsen, T. S., Lander, E. S., Schaffner, S. F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.027 · Cited by 480 · see citing works
Gupta, R. M., Hadaya, J., Trehan, A., Zekavat, S. M., Roselli, C., Klarin, D., Emdin, C. A., Hilvering, C. R. E., Bianchi, V., Mueller, C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.049 · Cited by 450 · see citing works
Self-citationContrasting the Genetic Architecture of 30 Complex Traits from Summary Association Data
Shi, H., Kichaev, G., & Pasaniuc, B. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.05.013 · Cited by 387 · see citing works
The Genetics of Transcription Factor DNA Binding Variation
Deplancke, B., Alpern, D., & Gardeux, V. (2016) · Cell · doi:10.1016/j.cell.2016.07.012 · Cited by 390 · see citing works
Yao, C., Chen, G., Song, C., Keefe, J., Mendelson, M., Huan, T., Sun, B. B., Laser, A., Maranville, J. C., Wu, H., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05512-x · Cited by 431 · see citing works
Mahdessian, H., Taxiarchis, A., Popov, S., Silveira, A., Franco-Cereceda, A., Hamsten, A., Eriksson, P., & van't Hooft, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323785111 · Cited by 369 · see citing works
Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits
Ulirsch, J. C., Nandakumar, S. K., Wang, L., Giani, F. C., Zhang, X., Rogov, P., Melnikov, A., McDonel, P., Do, R., Mikkelsen, T. S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.048 · Cited by 328 · see citing works
Porcu, E., Rüeger, S., Lepik, K., eQTLGen Consortium, Agbessi, M., Ahsan, H., Alves, I., Andiappan, A., Arindrarto, W., Awadalla, P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10936-0 · Cited by 322 · see citing works
A Role for Noncoding Variation in Schizophrenia
Roussos, P., Mitchell, A. C., Voloudakis, G., Fullard, J. F., Pothula, V. M., Tsang, J., Stahl, E. A., Georgakopoulos, A., Ruderfer, D. M., Charney, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.015 · Cited by 251 · see citing works
Self-citationEstimating the causal tissues for complex traits and diseases
GTEx Consortium, Ongen, H., Brown, A. A., Delaneau, O., Panousis, N. I., Nica, A. C., & Dermitzakis, E. T. (2017) · Nature Genetics · doi:10.1038/ng.3981 · Cited by 198 · see citing works
The study of eQTL variations by RNA-seq: from SNPs to phenotypes
Majewski, J., & Pastinen, T. (2011) · Trends in Genetics · doi:10.1016/j.tig.2010.10.006 · Cited by 232 · see citing works
Molecular and functional variation in iPSC-derived sensory neurons
HIPSCI Consortium, Schwartzentruber, J., Foskolou, S., Kilpinen, H., Rodrigues, J., Alasoo, K., Knights, A. J., Patel, M., Goncalves, A., Ferreira, R., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0005-8 · Cited by 223 · see citing works
Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity
Gazal, S., Weissbrod, O., Hormozdiari, F., Dey, K. K., Nasser, J., Jagadeesh, K. A., Weiner, D. J., Shi, H., Fulco, C. P., O’Connor, L. J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01087-y · Cited by 181 · see citing works
Warren, C. R., O’Sullivan, J. F., Friesen, M., Becker, C. E., Zhang, X., Liu, P., Wakabayashi, Y., Morningstar, J. E., Shi, X., Choi, J., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.01.010 · Cited by 191 · see citing works
Self-citationSIRT3 regulates mitochondrial protein acetylation and intermediary metabolism
Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., & Verdin, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010850 · Cited by 180 · see citing works
Holmes, M. V., Richardson, T. G., Ference, B. A., Davies, N. M., & Davey Smith, G. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00493-1 · Cited by 184 · see citing works
Lysosome biogenesis in health and disease
Bajaj, L., Lotfi, P., Pal, R., Ronza, A. D., Sharma, J., & Sardiello, M. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14564 · Cited by 153 · see citing works
3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes
Lu, Y., Quan, C., Chen, H., Bo, X., & Zhang, C. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1022 · Cited by 133 · see citing works
Conditional eQTL analysis reveals allelic heterogeneity of gene expression
Jansen, R., Hottenga, J.-J., Nivard, M. G., Abdellaoui, A., Laport, B., de Geus, E. J., Wright, F. A., Penninx, B. W. J. H., & Boomsma, D. I. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx043 · Cited by 141 · see citing works
Mora, S., Caulfield, M. P., Wohlgemuth, J., Chen, Z., Superko, H. R., Rowland, C. M., Glynn, R. J., Ridker, P. M., & Krauss, R. M. (2015) · Circulation · doi:10.1161/circulationaha.115.016857 · Cited by 126 · see citing works
Self-citationRNA sequencing reveals the role of splicing polymorphisms in regulating human gene expression
Lalonde, E., Ha, K. C. H., Wang, Z., Bemmo, A., Kleinman, C. L., Kwan, T., Pastinen, T., & Majewski, J. (2011) · Genome Research · doi:10.1101/gr.111211.110 · Cited by 111 · see citing works
Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo
Soccio, R. E., Chen, E. R., Rajapurkar, S. R., Safabakhsh, P., Marinis, J. M., Dispirito, J. R., Emmett, M. J., Briggs, E. R., Fang, B., Everett, L. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.025 · Cited by 117 · see citing works
Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
Yu Chen, H., Dina, C., Small, A. M., Shaffer, C. M., Levinson, R. T., Helgadóttir, A., Capoulade, R., Munter, H. M., Martinsson, A., Cairns, B. J., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad142 · Cited by 116 · see citing works
Self-citationPrediction of Causal Candidate Genes in Coronary Artery Disease Loci
Brænne, I., Civelek, M., Vilne, B., Di Narzo, A., Johnson, A. D., Zhao, Y., Reiz, B., Codoni, V., Webb, T. R., Foroughi Asl, H., et al. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.306108 · Cited by 109 · see citing works
Self-citationWu, Y., Zheng, Z., Visscher, P. M., & Yang, J. (2017) · Genome biology · doi:10.1186/s13059-017-1216-0 · Cited by 100 · see citing works
Genetic Regulatory Mechanisms of Smooth Muscle Cells Map to Coronary Artery Disease Risk Loci
Liu, B., Pjanic, M., Wang, T., Nguyen, T., Gloudemans, M., Rao, A., Castano, V. G., Nurnberg, S., Rader, D. J., Elwyn, S., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.08.001 · Cited by 94 · see citing works
Self-citationProgranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers
Meeter, L. H. H., Patzke, H., Loewen, G., Dopper, E. G. P., Pijnenburg, Y. A. L., van Minkelen, R., & van Swieten, J. C. (2016) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000447738 · Cited by 87 · see citing works
Munger, S. C., Raghupathy, N., Choi, K., Simons, A. K., Gatti, D. M., Hinerfeld, D. A., Svenson, K. L., Keller, M. P., Attie, A. D., Hibbs, M. A., et al. (2014) · Genetics · doi:10.1534/genetics.114.165886 · Cited by 85 · see citing works
Genetic influences on brain gene expression in rats selected for tameness and aggression
Heyne, H. O., Lautenschläger, S., Nelson, R., Besnier, F., Rotival, M., Cagan, A., Kozhemyakina, R., Plyusnina, I. Z., Trut, L., Carlborg, Ö., et al. (2014) · Genetics · doi:10.1534/genetics.114.168948 · Cited by 72 · see citing works
Sensitive detection of chromatin-altering polymorphisms reveals autoimmune disease mechanisms
del Rosario, R. C.-H., Poschmann, J., Rouam, S. L., Png, E., Khor, C. C., Hibberd, M. L., & Prabhakar, S. (2015) · Nature Methods · doi:10.1038/nmeth.3326 · Cited by 58 · see citing works
From genotype to phenotype in human atherosclerosis - recent findings
Holdt, L. M., & Teupser, D. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283654e7c · Cited by 62 · see citing works
Barbeira, A. N., Dickinson, S. P., Bonazzola, R., Zheng, J., Wheeler, H. E., Torres, J. M., Torstenson, E. S., Shah, K. P., Garcia, T., Edwards, T. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03621-1 · Cited by 69 · see citing works
Self-citationInsulin Regulation of Hepatic Lipid Homeostasis
Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49 · see citing works
Nakaoka, H., Gurumurthy, A., Hayano, T., Ahmadloo, S., Omer, W. H., Yoshihara, K., Yamamoto, A., Kurose, K., Enomoto, T., Akira, S., et al. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005893 · Cited by 46 · see citing works
Utility of genetic determinants of lipids and cardiovascular events in assessing risk
Holmes, M. V., Harrison, S., Talmud, P. J., Hingorani, A. D., & Humphries, S. E. (2011) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2011.6 · Cited by 44 · see citing works
Genetics of Polycystic Ovary Syndrome
Welt, C. K. (2021) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2020.10.006 · Cited by 43 · see citing works
Functional validation of new pathways in lipoprotein metabolism identified by human genetics
Bauer, R. C., Stylianou, I. M., & Rader, D. J. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834469b3 · Cited by 36 · see citing works
Self-citationMonogenic and Polygenic Models of Coronary Artery Disease
Muse, E. D., Chen, S.-F., & Torkamani, A. (2021) · Current Cardiology Reports · doi:10.1007/s11886-021-01540-0 · Cited by 27 · see citing works
A Non-coding HES1 Variant Predisposes Children to Congenital Heart Disease in Chinese Population
Song, Y., Chen, W., Huang, Z., Tian, G., Li, M., Zhao, Z., Feng, Z., Wu, F., Qian, M., Ma, X., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.631942 · Cited by 2 · see citing works
TFXcan reveals transcription factor programs driving GWAS loci
Adeluwa, T., Salazar-Magaña, S., Sumner, S., Gona, S., Nyasimi, F., Carbonetto, P., Baca, S. C., Freedman, M., Gusev, A., Liu, B., et al. (2026) · Cell Genomics · doi:10.1016/j.xgen.2026.101398
- Authors
- Musunuru, K., Strong, A., Frank-Kamenetsky, M., Lee, N. E., Ahfeldt, T., Sachs, K. V., Li, X., Li, H., Kuperwasser, N., Ruda, V. M., Pirruccello, J. P., Muchmore, B., Prokunina-Olsson, L., Hall, J. L., Schadt, E. E., Morales, C. R., Lund-Katz, S., Phillips, M. C., Wong, J., Cantley, W., Racie, T., Ejebe, K. G., Orho-Melander, M., Melander, O., Koteliansky, V., Fitzgerald, K., Krauss, R. M., Cowan, C. A., Kathiresan, S., & Rader, D. J.
- Affiliations
- Harvard University (US)
- University of Pennsylvania (US)
- Alnylam Pharmaceuticals (United States) (US)
- Broad Institute (US)
- National Institutes of Health (US)
- Sage Bionetworks (US)
- McGill University (CA)
- Children's Hospital of Philadelphia (US)
- Lund University (SE)
- Corresponding author
- Kathiresan, Sekar
- Rader, Daniel J.
- ORCID
- Venue
- Nature
- Published
- 2010-08
- Volume
- 466
- Issue
- 7307
- Pages
- 714-719
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3062476
- OpenAlex
- W2152435464
- Cited by
- 1,140
- References
- 37
- Citations by year
- 2026: 35 · 2025: 41 · 2024: 50 · 2023: 52 · 2022: 73 · 2021: 64 · 2020: 62 · 2019: 59 · 2018: 77 · 2017: 90 · 2016: 79 · 2015: 86 · 2014: 85 · 2013: 78 · 2012: 98
- FWCI
- 50.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (RC2HL101864, U01HL069757, P01HL059407, T32HL007954, K99HL098364)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- SORT1, non-coding variants, hepatic gene expression, plasma LDL cholesterol, VLDL secretion, lipoprotein metabolism, myocardial infarction, coronary artery disease, therapeutic target, cholesterol metabolism
- MeSH terms
- Sortilin, Animals, Base Sequence, Binding Sites, Cells, Cultured, Chromosomes, Human, Pair 1, Coronary Artery Disease, Europe, Gene Expression Regulation, Haplotypes, Humans, Lipids, Cholesterol, LDL, Lipoproteins, VLDL, Liver, Myocardial Infarction, Phenotype, Transcription, Genetic, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, CCAAT-Enhancer-Binding Proteins, Hepatocytes, Adaptor Proteins, Vesicular Transport, Mice, Genome-Wide Association Study, Gene Knockdown Techniques
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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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