Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity
Open accessPublished version of a preprint
Abstract
A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.
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?
Individuals homozygous for APOC3 loss-of-function variants have very low fasting TG levels, with no rise after a fat load.
“Furthermore, individuals who are homozygous for APOC3 LOF variants have very-low-fasting TG levels, with no rise after a fat load.9”
From Clinical review on triglycerides (2020) · cites this paper as [9]
Rare heterozygous loss-of-function variants associated with reduced TG levels show protection from ASCVD, providing evidence for a causal role of TG for ASCVD.
“Some rare heterozygous loss-of-function (LOF) variants are associated with reduced TG levels. These patients show protection from ASCVD providing important evidence for a causal role of TG for ASCVD.”
From Clinical review on triglycerides (2020) · cites this paper as [9]
Rare heterozygous loss-of-function variants in APOC3 are associated with approximately 50% reduced TG levels and significantly increased clearance of VLDL.
“For instance, rare heterozygous LOF variants in APOC3 encoding apo C-III are associated with ∼50% reduced TG levels and significantly increased clearance of very-low-density lipoprotein (VLDL).8,9”
From Clinical review on triglycerides (2020) · cites this paper as [9]
Apo C-III is a genetically validated target to reduce ASCVD risk.
“and is a genetically validated target to reduce ASCVD risk.8–10,64–66”
From Clinical review on triglycerides (2020) · cites this paper as [9]
Studies in populations with high rates of consanguinity make it possible to identify individuals homozygous for otherwise rare loss-of-function alleles, forming the basis for a human knockout project.
“In addition, studies in populations with high rates of consanguinity make it possible to identify individuals homozygous for otherwise rare loss-of-function alleles, the basis for a ‘human knockout’ project to systematically investigate the phenotypic consequences of gene disruption in humans53,54.”
From A brief history of human disease genetics (2020) · cites this paper as [54]
Efforts to probe clinical consequences of coding alleles with large phenotypic effects, particularly null alleles, in humans and animal models represent powerful strategies for extending functional analyses to the whole-body level.
“Efforts to probe the clinical consequences of coding alleles with large phenotypic effects (particularly null alleles) in humans53,54 and across diverse animal models116 represent powerful strategies for extending functional analyses to the whole-body level.”
From A brief history of human disease genetics (2020) · cites this paper as [54]
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
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
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-citationThe Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
Self-citationA framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,216 · see citing works
Self-citationPrincipal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Self-citationVan der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687 · see citing works
Self-citationRobust relationship inference in genome-wide association studies
Manichaikul, A., Mychaleckyj, J. C., Rich, S. S., Daly, K., Sale, M., & Chen, W.-M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq559 · Cited by 3,541 · see citing works
Simplified calculation of body surface area
(1987) · New England Journal of Medicine · doi:10.1056/nejm198710223171717 · Cited by 3,238 · see citing works
Synaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746 · see citing works
Self-citationCoefficients of Inbreeding and Relationship
Wright, S. (1922) · The American Naturalist · doi:10.1086/279872 · Cited by 2,307 · see citing works
Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery
Gold, L., Ayers, D., Bertino, J., Bock, C., Bock, A., Brody, E. N., Carter, J., Dalby, A. B., Eaton, B. E., Fitzwater, T., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015004 · Cited by 1,754 · see citing works
Identification and characterization of essential genes in the human genome
Wang, T., Birsoy, K., Hughes, N. W., Krupczak, K. M., Post, Y., Wei, J. J., Lander, E. S., & Sabatini, D. M. (2015) · Science · doi:10.1126/science.aac7041 · Cited by 1,617 · see citing works
Self-citationEvolution and functional impact of rare coding variation from deep sequencing of human exomes
Tennessen, J. A., Bigham, A. W., O’Connor, T. D., Fu, W., Kenny, E. E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G., et al. (2012) · Science · doi:10.1126/science.1219240 · Cited by 1,613 · see citing works
Self-citationDeriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor
McLaren, W. M., Yates, B., Ríos, D., Chen, Y., Flicek, P., & Cunningham, F. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq330 · Cited by 1,586 · see citing works
A polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385 · see citing works
Self-citationA Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes
MacArthur, D. G., Balasubramanian, S., Frankish, A., Huang, N., Morris, J., Walter, K., Jostins, L., Habegger, L., Pickrell, J. K., Montgomery, S. B., et al. (2012) · Science · doi:10.1126/science.1215040 · Cited by 1,272 · see citing works
Self-citationConcept of Vulnerable/Unstable Plaque
Finn, A. V., Nakano, M., Narula, J., Kolodgie, F. D., & Virmani, R. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179739 · Cited by 1,193 · see citing works
Loss-of-Function Mutations in <i>APOC3,</i> Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071 · see citing works
Purification of Nucleic Acids by Extraction with Phenol:Chloroform
Sambrook, J., & Russell, D. W. (2006) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot4455 · Cited by 1,047 · see citing works
A framework for the interpretation of de novo mutation in human disease
Samocha, K. E., Robinson, E. B., Sanders, S. J., Stevens, C., Sabo, A., McGrath, L. M., Kosmicki, J. A., Rehnström, K., Mallick, S., Kirby, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3050 · Cited by 979 · see citing works
Self-citationLoss-of-Function Mutations in <i>APOC3</i> and Risk of Ischemic Vascular Disease
Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308027 · Cited by 919 · see citing works
Homozygosity Mapping: A Way to Map Human Recessive Traits with the DNA of Inbred Children
Lander, E. S., & Botstein, D. (1987) · Science · doi:10.1126/science.2884728 · Cited by 877 · see citing works
Self-citationProtein function in the post-genomic era
Eisenberg, D. S., Marcotte, E. M., Xénarios, I., & Yeates, T. O. (2000) · Nature · doi:10.1038/35015694 · Cited by 749 · see citing works
Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., et al. (2008) · Science · doi:10.1126/science.1161524 · Cited by 688 · see citing works
Standiford, T. J., Kunkel, S. L., Aseem Basha, M., Chensue, S. W., Lynch, J. P., Toews, G. B., Westwick, J. K., & Strieter, R. M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114928 · Cited by 687 · see citing works
Fisher, S., Barry, A. J., Abreu, J., Minie, B., Nolan, J., Delorey, T. M., Young, G., Fennell, T. J., Allen, A., Ambrogio, L., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-1-r1 · Cited by 683 · see citing works
Self-citationExome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction
Do, R., Stitziel, N. O., Won, H.-H., Jørgensen, A. B., Duga, S., Angelica Merlini, P., Kiezun, A., Farrall, M., Goel, A., Zuk, O., et al. (2015) · Nature · doi:10.1038/nature13917 · Cited by 650 · see citing works
Self-citationDarapladib for Preventing Ischemic Events in Stable Coronary Heart Disease
The STABILITY Investigators (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315878 · Cited by 579 · see citing works
Lipid-Related Markers and Cardiovascular Disease Prediction
The Emerging Risk Factors Collaboration (2012) · JAMA · doi:10.1001/jama.2012.6571 · Cited by 539 · see citing works
DIAGRAM, Kooner, J. S., MuTHER, Saleheen, D., Sim, X., Sehmi, J., Zhang, W., Frossard, P., Been, L. F., Chia, K., et al. (2011) · Nature Genetics · doi:10.1038/ng.921 · Cited by 531 · see citing works
Self-citationAntisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia
Gaudet, D., Alexander, V. J., Baker, B. F., Brisson, D., Tremblay, K., Singleton, W., Geary, R. S., Hughes, S. G., Viney, N. J., Graham, M. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1400283 · Cited by 528 · see citing works
Wang, G.-X., Zhao, X.-Y., Meng, Z., Kern, M., Dietrich, A., Chen, Z., Cozacov, Z., Zhou, D., Okunade, A. L., Su, X., et al. (2014) · Nature Medicine · doi:10.1038/nm.3713 · Cited by 508 · see citing works
Targeting APOC3 in the familial chylomicronemia syndrome
Gaudet, D., Brisson, D., Tremblay, K., Alexander, V. J., Singleton, W., Hughes, S. G., Geary, R. S., Baker, B. F., Graham, M. J., Crooke, R. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400284 · Cited by 491 · see citing works
Jun, G., Flickinger, M., Hetrick, K. N., Romm, J. M., Doheny, K. F., Abecasis, G. R., Boehnke, M., & Kang, H. M. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.09.004 · Cited by 484 · see citing works
O’Donoghue, M. L., Braunwald, E., White, H. D., Steen, D. P., Lukas, M. A., Tarka, E., Steg, P. G., Hochman, J. S., Bode, C., Maggioni, A. P., et al. (2014) · JAMA · doi:10.1001/jama.2014.11061 · Cited by 456 · see citing works
The epidermal growth factor receptor ligands at a glance
Schneider, M. R., & Wolf, E. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21635 · Cited by 447 · see citing works
Fazzio, T. G., Huff, J. T., & Panning, B. (2008) · Cell · doi:10.1016/j.cell.2008.05.031 · Cited by 436 · see citing works
Graham, M. J., Lee, R. G., Bell, T. A., Fu, W., Mullick, A. E., Alexander, V. J., Singleton, W., Viney, N., Geary, R., Su, J., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300367 · Cited by 377 · see citing works
Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery
Greater Middle East Variome Consortium, Scott, E. M., Halees, A., Itan, Y., Spencer, E. G., He, Y., Azab, M. A., Gabriel, S. B., Belkadi, A., Boisson, B., et al. (2016) · Nature Genetics · doi:10.1038/ng.3592 · Cited by 376 · see citing works
Self-citationThe Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease
Eppig, J. T., Blake, J. A., Bult, C. J., Kadin, J. A., Richardson, J. E., & The Mouse Genome Database Group (2014) · Nucleic Acids Research · doi:10.1093/nar/gku967 · Cited by 358 · see citing works
Reproductive Behavior and Health in Consanguineous Marriages
Bittles, A. H., Mason, W. M., Greene, J., & Rao, N. A. (1991) · Science · doi:10.1126/science.2028254 · Cited by 331 · see citing works
The p400 Complex Is an Essential E1A Transformation Target
Fuchs, M., Gerber, J. D., Drapkin, R., Sif, S., Ikura, T., Ogryzko, V. V., Lane, W. S., Nakatani, Y., & Livingston, D. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00450-0 · Cited by 328 · see citing works
Genetic counselling and customary consanguineous marriage
Modell, B., & Darr, A. (2002) · Nature Reviews Genetics · doi:10.1038/nrg754 · Cited by 297 · see citing works
Health and population effects of rare gene knockouts in adult humans with related parents
Narasimhan, V. M., Hunt, K. A., Mason, D., Baker, C. L., Karczewski, K. J., Barnes, M. R., Barnett, A. H., Bates, C., Bellary, S., Bockett, N. A., et al. (2016) · Science · doi:10.1126/science.aac8624 · Cited by 286 · see citing works
Self-citationIdentification of a large set of rare complete human knockouts
Sulem, P., Helgason, H., Oddson, A., Stefansson, H., Gudjonsson, S. A., Zink, F., Hjartarson, E., Sigurdsson, G. T., Jonasdottir, A., Jonasdottir, A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3243 · Cited by 220 · see citing works
NHERF1 Mutations and Responsiveness of Renal Parathyroid Hormone
Karim, Z., Gérard, B., Bakouh, N., Alili, R., Leroy, C., Beck, L., Silve, C., Planelles, G., Ureña, P., Grandchamp, B., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802836 · Cited by 207 · see citing works
From Mouse to Human: Evolutionary Genomics Analysis of Human Orthologs of Essential Genes
Georgi, B., Voight, B. F., & Bućan, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003484 · Cited by 186 · see citing works
Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium
Brown, S. D. M., & Moore, M. W. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009878 · Cited by 156 · see citing works
Population Genetic Structure of the People of Qatar
Hunter-Zinck, H., Musharoff, S. A., Salit, J., Alali, K., Chouchane, L., Gohar, A., Matthews, R., Butler, M. W., Fuller, J. A., Hackett, N. R., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.05.018 · Cited by 127 · see citing works
Christiansen, D., Milland, J., Mouhtouris, E., Vaughan, H. A., Pellicci, D. G., McConville, M. J., Godfrey, D. I., & Sandrin, M. S. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060172 · Cited by 115 · see citing works
Saleheen, D., Zaidi, M. A., Rasheed, A., Ahmad, U., Hakeem, A., Murtaza, M., Kayani, W. T., FARUQUI, A. M. A., Kundi, A., Zaman, K. S., et al. (2009) · European Journal of Epidemiology · doi:10.1007/s10654-009-9334-y · Cited by 107 · see citing works
Self-citationMurtazina, R., Kovbasnjuk, O. N., Zachos, N. C., Li, X., Chen, Y., Hubbard, A. L., Hogema, B. M., Steplock, D., Seidler, U. E., Hoque, K. M., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701910200 · Cited by 77 · see citing works
Apolipoprotein C-III: Going Back to the Future for a Lipid Drug Target
Huff, M. W., & Hegele, R. A. (2013) · Circulation Research · doi:10.1161/circresaha.113.301464 · Cited by 70 · see citing works
Murray, I. A., Coupland, K., Smith, J. A., Ansell, I. D., & Long, R. G. (2000) · British Journal Of Nutrition · doi:10.1017/s0007114500000313 · Cited by 53 · see citing works
Carr, B., Wan, J., Hines, R. N., & Yost, G. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300319200 · Cited by 45 · see citing works
Casu, A., Echeverri, G. J., Bottino, R., van der Windt, D. J., He, J., Ekser, B., Ball, S. F., Ayares, D., & Cooper, D. K. C. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2010.00572.x · Cited by 36 · see citing works
Coronary Heart Disease and Genetic Variants with Low Phospholipase A2 Activity
Polfus, L. M., Gibbs, R. A., & Boerwinkle, E. (2015) · New England Journal of Medicine · doi:10.1056/nejmc1409673 · Cited by 36 · see citing works
Gregson, J., Freitag, D. F., Surendran, P., Stitziel, N. O., Chowdhury, R., Burgess, S., Kaptoge, S. K., Gao, P., Staley, J. R., Willeit, P., et al. (2016) · European Journal of Preventive Cardiology · doi:10.1177/2047487316682186 · Cited by 35 · see citing works
Self-citationValidity of abbreviated oral fat tolerance tests for assessing postprandial lipemia
Maraki, M. I., Aggelopoulou, N., Christodoulou, N., Katsarou, C., Anapliotis, P., Kavouras, S. A., Panagiotakos, D. B., & Sidossis, L. S. (2011) · Clinical Nutrition · doi:10.1016/j.clnu.2011.05.003 · Cited by 32 · see citing works
Glucose intolerance in a xenotransplantation model: studies in alpha‐gal knockout mice
Dahl, K., Buschard, K., Gram, D. X., d’Apice, A. J. F., & Hansen, A. K. (2006) · Apmis · doi:10.1111/j.1600-0463.2006.apm_393.x · Cited by 11 · see citing works
Gregson, J., Freitag, D. F., Surendran, P., Stitziel, N. O., Chowdhury, R., Burgess, S., Kaptoge, S. K., Gao, P., Staley, J. R., Willeit, P., et al. (2016) · University of Regensburg Publication Server (University of Regensburg) · doi:10.17863/cam.8479 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
2 of the 64 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Self-citationThe Missing Diversity in Human Genetic Studies
Sirugo, G., Williams, S. M., & Tishkoff, S. A. (2019) · Cell · doi:10.1016/j.cell.2019.02.048 · Cited by 1,516 · see citing works
Runs of homozygosity: windows into population history and trait architecture
Ceballos, F. C., Joshi, P. K., Clark, D. W., Ramsay, M., & Wilson, J. F. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.109 · Cited by 1,006 · see citing works
Vujkovic, M., Keaton, J. M., Lynch, J. A., Miller, D. R., Zhou, J., Tcheandjieu, C., Huffman, J. E., Assimes, T. L., Lorenz, K., Zhu, X., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0637-y · Cited by 741 · see citing works
Self-citationA 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-citationGenetics 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-citationExome sequencing and characterization of 49,960 individuals in the UK Biobank
Van Hout, C. V., Tachmazidou, I., Backman, J. D., Hoffman, J. D., Liu, D., Pandey, A. K., Gonzaga-Jauregui, C., Khalid, S., Ye, B., Banerjee, N., et al. (2020) · Nature · doi:10.1038/s41586-020-2853-0 · Cited by 561 · see citing works
Clinical review on triglycerides
Laufs, U., Parhofer, K. G., Ginsberg, H. N., & Hegele, R. A. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz785 · Cited by 544 · see citing works
The GenomeAsia 100K Project enables genetic discoveries across Asia
Wall, J. D., Stawiski, E. W., Ratan, A., Kim, H. L., Kim, C., Gupta, R. K., Suryamohan, K., Gusareva, E. S., Purbojati, R. W., Bhangale, T., et al. (2019) · Nature · doi:10.1038/s41586-019-1793-z · Cited by 454 · see citing works
Self-citationKim, M. Y., Yu, K., Kenderian, S. S., Ruella, M., Chen, S., Shin, T., Aljanahi, A. A., Schreeder, D. M., Klichinsky, M., Shestova, O. E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.013 · Cited by 458 · see citing works
Volgman, A. S., Palaniappan, L. S., Aggarwal, N. T., Gupta, M., Khandelwal, A., Krishnan, A. V., Lichtman, J. H., Mehta, L. S., Patel, H. N., Shah, K. S., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000580 · Cited by 552 · see citing works
Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis
Bick, A. G., Pirruccello, J. P., Griffin, G. K., Gupta, N., Gabriel, S., Saleheen, D., Libby, P., Kathiresan, S., & Natarajan, P. (2019) · Circulation · doi:10.1161/circulationaha.119.044362 · Cited by 418 · see citing works
Self-citationThe complexity of tau in Alzheimer’s disease
Naseri, N. N., Wang, H., Guo, J. D., Sharma, M., & Luo, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.022 · Cited by 374 · see citing works
The impact of rare and low-frequency genetic variants in common disease
Bomba, L., Walter, K., & Soranzo, N. (2017) · Genome biology · doi:10.1186/s13059-017-1212-4 · Cited by 342 · see citing works
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
Funcke, J., & Scherer, P. E. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r094060 · Cited by 337 · see citing works
The Missing Diversity in Human Genetic Studies
Sirugo, G., Williams, S. M., & Tishkoff, S. A. (2019) · Cell · doi:10.1016/j.cell.2019.04.032 · Cited by 317 · see citing works
Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation
Zewinger, S., Reiser, J., Jankowski, V., Alansary, D., Hahm, E., Triem, S., Klug, M., Schunk, S. J., Schmit, D., Kramann, R., et al. (2020) · Nature Immunology · doi:10.1038/s41590-019-0548-1 · Cited by 280 · see citing works
High-density lipoproteins, reverse cholesterol transport and atherogenesis
Pownall, H. J., Rosales, C., Gillard, B. K., & Gotto, A. M. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00538-z · Cited by 250 · see citing works
Genetics of Common, Complex Coronary Artery Disease
Musunuru, K., & Kathiresan, S. (2019) · Cell · doi:10.1016/j.cell.2019.02.015 · Cited by 241 · see citing works
Self-citationBartha, I., di Iulio, J., Venter, J. C., & Telenti, A. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.75 · Cited by 239 · see citing works
Settling the score: variant prioritization and Mendelian disease
Eilbeck, K. L., Quinlan, A. R., & Yandell, M. D. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.52 · Cited by 221 · see citing works
From target discovery to clinical drug development with human genetics
Trajanoska, K., Bhérer, C., Taliun, D., Zhou, S., Richards, J. B., & Mooser, V. (2023) · Nature · doi:10.1038/s41586-023-06388-8 · Cited by 222 · see citing works
Chadwick, A. C., Wang, X., & Musunuru, K. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309881 · Cited by 218 · see citing works
Hemingway, H., Asselbergs, F. W., Danesh, J., Dobson, R., Maniadakis, N., Maggioni, A. P., van Thiel, G. J. M. W., Cronin, M., Brobert, G., Vardas, P. E., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx487 · Cited by 212 · see citing works
Self-citationPatel, A. P., Wang, M., Kartoun, U., Ng, K., & Khera, A. V. (2021) · Circulation · doi:10.1161/circulationaha.120.052430 · Cited by 210 · see citing works
Insights into genetics, human biology and disease gleaned from family based genomic studies
Posey, J. E., O’Donnell‐Luria, A., Chong, J. X., Harel, T., Jhangiani, S. N., Coban‐Akdemir, Z., Buyske, S. G., Pehli̇van, D., Carvalho, C. M. B., Baxter, S. M., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0408-7 · Cited by 198 · see citing works
Self-citationThe Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans
Borén, J., Packard, C. J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00474 · Cited by 196 · see citing works
Evaluating drug targets through human loss-of-function genetic variation
Minikel, E. V., Karczewski, K. J., Martin, H. C., Cummings, B. B., Whiffin, N., Rhodes, D., Alföldi, J., Trembath, R. C., van Heel, D. A., Daly, M. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2267-z · Cited by 182 · see citing works
Self-citationStroke genetics: discovery, biology, and clinical applications
Dichgans, M., Pulit, S. L., & Rosand, J. M. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30043-2 · Cited by 184 · see citing works
Lipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171 · see citing works
Unique roles of rare variants in the genetics of complex diseases in humans
Momozawa, Y., & Mizukami, K. (2021) · Journal of Human Genetics · doi:10.1038/s10038-020-00845-2 · Cited by 161 · see citing works
From Peas to Disease: Modifier Genes, Network Resilience, and the Genetics of Health
Riordan, J. D., & Nadeau, J. H. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.004 · Cited by 154 · see citing works
Estimating the selective effects of heterozygous protein-truncating variants from human exome data
Cassa, C. A., Weghorn, D., Balick, D. J., Jordan, D. M., Nusinow, D. P., Samocha, K. E., O’Donnell‐Luria, A., MacArthur, D. G., Daly, M. J., Beier, D. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3831 · Cited by 151 · see citing works
Self-citationPrecise modulation of transcription factor levels identifies features underlying dosage sensitivity
Naqvi, S., Kim, S., Hoskens, H., Matthews, H. S., Spritz, R. A., Klein, O. D., Hallgrímsson, B., Swigut, T., Claes, P., Pritchard, J. K., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01366-2 · Cited by 132 · see citing works
Associations of autozygosity with a broad range of human phenotypes
Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12283-6 · Cited by 150 · see citing works
Self-citationAddressing dyslipidemic risk beyond LDL-cholesterol
Tall, A. R., Thomas, D. G., Gonzalez-Cabodevilla, A. G., & Goldberg, I. J. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148559 · Cited by 150 · see citing works
Significant sparse polygenic risk scores across 813 traits in UK Biobank
Tanigawa, Y., Qian, J., Venkataraman, G. R., Justesen, J. M., Li, R., Tibshirani, R. J., Hastie, T. J., & Rivas, M. A. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1010105 · Cited by 148 · see citing works
Yamauchi, T., Masuda, T., Canver, M. C., Seiler, M., Semba, Y., Shboul, M., Al‐Raqad, M., Maeda, M., Schoonenberg, V. A. C., Cole, M. A., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.012 · Cited by 134 · see citing works
Kwan, T., Wong, S. S., Hong, Y., Kanaya, A. M., Khan, S. S., Hayman, L. L., Shah, S. H., Welty, F. K., DEEDWANIA, P. C., Khaliq, A., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001145 · Cited by 139 · see citing works
Carrier screening for recessive disorders
Antonarakis, S. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0134-2 · Cited by 129 · see citing works
Van Hout, C. V., Tachmazidou, I., Backman, J. D., Hoffman, J. X., Ye, B., Pandey, A. K., Gonzaga-Jauregui, C., Khalid, S., Liu, D., Banerjee, N., et al. (2019) · doi:10.1101/572347 · Cited by 110 · see citing works
Finer, S., Martin, H. C., Khan, A., Hunt, K. A., MacLaughlin, B., Ahmed, Z., Ashcroft, R. E., Durham, C., MacArthur, D. G., McCarthy, M. I., et al. (2019) · International Journal of Epidemiology · doi:10.1093/ije/dyz174 · Cited by 116 · see citing works
Self-citationMedical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study
DeBoever, C., Tanigawa, Y., Lindholm, M. E., McInnes, G., Lavertu, A., Ingelsson, E., Chang, C. C., Ashley, E. A., Bustamante, C. D., Daly, M. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03910-9 · Cited by 122 · see citing works
Self-citationThe effect of LRRK2 loss-of-function variants in humans
Whiffin, N., Armean, I. M., Kleinman, A., Marshall, J. L., Minikel, E. V., Goodrich, J. K., Quaife, N. M., Cole, J. B., Wang, Q. S., Karczewski, K. J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0893-5 · Cited by 125 · see citing works
Self-citationThe Genetic Basis of Metabolic Disease
Barroso, I., & McCarthy, M. I. (2019) · Cell · doi:10.1016/j.cell.2019.02.024 · Cited by 124 · see citing works
Schöneberg, T., & Liebscher, I. (2020) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000011 · Cited by 127 · see citing works
Trehalose and its applications in the food industry
Chen, A., Tapia, H., Goddard, J. M., & Gibney, P. A. (2022) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.13048 · Cited by 116 · see citing works
A deep catalogue of protein-coding variation in 983,578 individuals
Sun, K. Y., Bai, X., Chen, S., Bao, S., Zhang, C., Kapoor, M., Backman, J., Joseph, T., Maxwell, E., Mitra, G., et al. (2024) · Nature · doi:10.1038/s41586-024-07556-0 · Cited by 127 · see citing works
Wulff, A. B., Nordestgaard, B. G., & Tybjærg‐Hansen, A. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310473 · Cited by 111 · see citing works
Arnadottir, G. A., Norddahl, G. L., Guðmundsdóttir, S., Agustsdottir, A. B., Sigurðsson, S., Jensson, B. Ö., Bjarnadóttir, K., Theódórs, F., Benónísdóttir, S., Ivarsdottir, E. V., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06964-x · Cited by 109 · see citing works
Simons, Y. B., & Sella, G. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.09.006 · Cited by 103 · see citing works
Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes
Kanter, J. E., Shao, B., Kramer, F., Barnhart, S., Shimizu‐Albergine, M., Vaisar, T., Graham, M. J., Crooke, R. M., Manuel, C. R., Haeusler, R. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127308 · Cited by 105 · see citing works
Human genetics of infectious diseases: Unique insights into immunological redundancy
Casanova, J., & Abel, L. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.12.008 · Cited by 104 · see citing works
The genetic structure of the Turkish population reveals high levels of variation and admixture
Kars, M. E., Başak, A. N., Onat, O. E., Bilgüvar, K., Choi, J., Itan, Y., Çağlar, C., Palvadeau, R. J., Casanova, J., Cooper, D. N., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2026076118 · Cited by 107 · see citing works
Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD
Taskinen, M., Packard, C. J., & Borén, J. (2019) · Current Atherosclerosis Reports · doi:10.1007/s11883-019-0791-9 · Cited by 104 · see citing works
Phenotypes associated with genes encoding drug targets are predictive of clinical trial side effects
Nguyen, P. A., Born, D. A., Deaton, A. M., Nioi, P., & Ward, L. D. (2019) · Nature Communications · doi:10.1038/s41467-019-09407-3 · Cited by 104 · see citing works
Effects of <i>APOC3</i> Heterozygous Deficiency on Plasma Lipid and Lipoprotein Metabolism
Reyes-Soffer, G., Sztalryd, C., Horenstein, R. B., Holleran, S., Matveyenko, A., Thomas, T., Nandakumar, R., Ngai, C., Karmally, W., Ginsberg, H. N., et al. (2019) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.118.311476 · Cited by 97 · see citing works
Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding
Sniderman, A. D., Couture, P., Martin, S. S., DEGRAAF, J., Lawler, P. R., Cromwell, W. C., Wilkins, J. T., & Thanassoulis, G. (2018) · Journal of Lipid Research · doi:10.1194/jlr.r082271 · Cited by 91 · see citing works
Using human genetics to improve safety assessment of therapeutics
Carss, K., Deaton, A. M., Río-Espínola, A. D., Diogo, D., Fielden, M. R., Kulkarni, D. A., Moggs, J. G., Newham, P., Nelson, M. R., Sistare, F. D., et al. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00561-w · Cited by 88 · see citing works
The Mouse Lemur, a Genetic Model Organism for Primate Biology, Behavior, and Health
Ezran, C., Karanewsky, C. J., Pendleton, J. L., Sholtz, A., Biermann, M. R., Willick, J., Razafindrakoto, A., Zohdy, S., Albertelli, M. A., & Krasnow, M. A. (2017) · Genetics · doi:10.1534/genetics.116.199448 · Cited by 81 · see citing works
Less Is More, Natural Loss-of-Function Mutation Is a Strategy for Adaptation
Xu, Y., & Guo, Y. (2020) · Plant Communications · doi:10.1016/j.xplc.2020.100103 · Cited by 74 · see citing works
The virtuous cycle of human genetics and mouse models in drug discovery
Nadeau, J. H., & Auwerx, J. H. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0009-9 · Cited by 71 · see citing works
Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Corbin, L. J., Tan, V. Y., Hughes, D. A., Wade, K. H., Paul, D. S., Tansey, K. E., Butcher, F. C., Dudbridge, F., Howson, J. M. M., Jallow, M. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03109-y · Cited by 66 · see citing works
Self-citationPerenthaler, E., Nikoncuk, A., Yousefi, S., Berdowski, W. M., Alsagob, M., Čapo, I., van der Linde, H. C., van den Berg, P., Jacobs, E. H., Putar, D., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02109-6 · Cited by 70 · see citing works
Whole genome sequence analysis of blood lipid levels in >66,000 individuals
Selvaraj, M. S., Li, X., Li, Z., Pampana, A., Zhang, D. Y., Park, J., Aslibekyan, S. W., Bis, J. C., Brody, J. A., Cade, B. E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33510-7 · Cited by 67 · see citing works
Self-citationProfiling and Leveraging Relatedness in a Precision Medicine Cohort of 92,455 Exomes
Staples, J. C., Maxwell, E. K., Gosalia, N., Gonzaga-Jauregui, C. G., Snyder, C., Hawes, A. C., Penn, J., Ulloa, R. H., Bai, X., Lopez, A. E., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.03.012 · Cited by 66 · see citing works
Butler, A. A., Zhang, J., Price, C. A., Stevens, J. R., Graham, J. L., Stanhope, K. L., King, S. M., Krauss, R. M., Bremer, A. A., & Havel, P. J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007528 · Cited by 69 · see citing works
Self-citationLi, Q., Ren, Z., Cao, K., Li, M. M., Wang, K., & Zhou, Y. (2022) · Science Advances · doi:10.1126/sciadv.abj1624 · Cited by 66 · see citing works
Genetic-Driven Druggable Target Identification and Validation
Floris, M., Olla, S., Schlessinger, D., & Cucca, F. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.04.004 · Cited by 64 · see citing works
Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis
Natarajan, P., Jaiswal, S., & Kathiresan, S. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.118.001926 · Cited by 63 · see citing works
Self-citationUnderstanding the Hidden Complexity of Latin American Population Isolates
Mooney, J. A., Huber, C. D., Service, S. K., Sul, J. H., Marsden, C. D., Zhang, Z., Sabatti, C., Ruiz‐Linares, A., Bedoya, G., Freimer, N. B., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.09.013 · Cited by 63 · see citing works
Harshfield, E. L., Fauman, E. B., Stacey, D., Paul, D. S., Ziemek, D., Ong, R. M. Y., Danesh, J., Butterworth, A. S., Rasheed, A., Sattar, T., et al. (2021) · BMC Medicine · doi:10.1186/s12916-021-02087-1 · Cited by 64 · see citing works
Self-citationExploring apolipoprotein C-III: pathophysiological and pharmacological relevance
Packard, C. J., Pirillo, A., Tsimikas, S., Ference, B. A., & Catapano, A. L. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad177 · Cited by 65 · see citing works
Clinical use of polygenic risk scores: current status, barriers and future directions
Kullo, I. J. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00900-8 · Cited by 68 · see citing works
New Human Chromosomal Sites with “Safe Harbor” Potential for Targeted Transgene Insertion
Pellenz, S., Phelps, M., Tang, W., Hovde, B. T., Sinit, R. B., Fu, W., Li, H., Chen, E. Y., & Monnat, R. J. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.169 · Cited by 61 · see citing works
Xu, Y., Niu, X., Li, X., He, W., Chen, J., Zou, Y.-P., Wu, Q., Zhang, Y. E., Busch, W., & Guo, Y. (2019) · The Plant Cell · doi:10.1105/tpc.18.00791 · Cited by 59 · see citing works
McGregor, T. L., Hunt, K. A., Yee, E., Mason, D., Nioi, P., Ticau, S., Pelosi, M., Loken, P. R., Finer, S., Lawlor, D. A., et al. (2020) · eLife · doi:10.7554/elife.54363 · Cited by 57 · see citing works
Self-citationFunctional effects of protein variants
Vihinen, M. (2020) · Biochimie · doi:10.1016/j.biochi.2020.10.009 · Cited by 53 · see citing works
Kinzina, E., Podolskiy, D. I., Dmitriev, S. E., & Gladyshev, V. N. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.091 · Cited by 55 · see citing works
Personalized medicine for cardiovascular diseases
Tada, H., Fujino, N., Nomura, A., Nakanishi, C., Hayashi, K., Takamura, M., & Kawashiri, M. (2020) · Journal of Human Genetics · doi:10.1038/s10038-020-0818-7 · Cited by 54 · see citing works
Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes
Razali, R., Rodríguez-Flores, J. L., Ghorbani, M., Naeem, H., Aamer, W., ALIYEV, E. E., Jubran, A., Qatar Genome Project Management, Ismail, S. I., Al‐Muftah, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25287-y · Cited by 53 · see citing works
Apolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL
Larsson, M., Allan, C. M., Jung, R. S., Heizer, P. J., Beigneux, A. P., Young, S. G., & Fong, L. G. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m078220 · Cited by 54 · see citing works
ApoCIII: A multifaceted protein in cardiometabolic disease
D’Erasmo, L., Costanzo, A. D., Gallo, A., Bruckert, É., & Arca, M. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154395 · Cited by 52 · see citing works
Sadowski, M., Kraft, A., Szałaj, P., Wlasnowolski, M., Tang, Z., Ruan, Y., & Plewczyński, D. (2019) · Genome biology · doi:10.1186/s13059-019-1728-x · Cited by 50 · see citing works
Basu, D., & Bornfeldt, K. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00504 · Cited by 51 · see citing works
Human genetics and its impact on cardiovascular disease
Tada, H., Fujino, N., Hayashi, K., Kawashiri, M., & Takamura, M. (2021) · Journal of Cardiology · doi:10.1016/j.jjcc.2021.09.005 · Cited by 51 · see citing works
Björnson, E., Packard, C. J., Adiels, M., Andersson, L., Matikainen, N., Söderlund, S., Kahri, J., Hakkarainen, A., Lundbom, N., Lundbom, J., et al. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13017 · Cited by 46 · see citing works
Erzurumluoglu, A. M., Shihab, H. A., Rodrı́guez, S., Gaunt, T. R., & Day, I. N. M. (2016) · Annals of Human Genetics · doi:10.1111/ahg.12150 · Cited by 46 · see citing works
South Asian medical cohorts reveal strong founder effects and high rates of homozygosity
Wall, J. D., Sathirapongsasuti, J. F., Gupta, R. K., Rasheed, A., Radha, V., Belsare, S., Menon, R., Phalke, S., Mittal, A., Fang, J. Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38766-1 · Cited by 43 · see citing works
Self-citationGenetic variation in the Middle East—an opportunity to advance the human genetics field
Tayoun, A. N. A., & Rehm, H. L. (2020) · Genome Medicine · doi:10.1186/s13073-020-00821-7 · Cited by 45 · see citing works
The multifaceted role of WNT signaling in Alzheimer’s disease onset and age-related progression.
Kostes, W. W., & Brafman, D. A. (2023) · Cells · doi:10.3390/cells12081204 · Cited by 43 · see citing works
Inactivation of ApoC3 by CRISPR/Cas9 Protects Against Atherosclerosis in Hamsters
Guo, M., Xu, Y., Zhao, D., Zhou, Z., Cong, N., Gao, M., Huang, W. Y., Wang, Y., Liu, C., & Xian, X. (2020) · Circulation Research · doi:10.1161/circresaha.120.317686 · Cited by 44 · see citing works
Translational Medicine in the Era of Big Data and Machine Learning
Weintraub, W. S., Fahed, A. C., & Rumsfeld, J. S. (2018) · Circulation Research · doi:10.1161/circresaha.118.313944 · Cited by 44 · see citing works
Wang, H., Huang, X., Xu, P., Liu, X., Zhou, Z., Wang, F., Li, J., Wang, Y., Xian, X., Liu, C., et al. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154740 · Cited by 42 · see citing works
Implementation of public health genomics in Pakistan
Riaz, M., Tiller, J. M., Ajmal, M., Azam, M., Qamar, R., & Lacaze, P. A. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0428-z · Cited by 42 · see citing works
Abeler‐Dörner, L., Laing, A. G., Lorenc, A., Ushakov, D. S., Clare, S., Speak, A. O., Correa, M. A. D., White, J. K., Ramírez‐Solis, R., Saran, N., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0549-0 · Cited by 42 · see citing works
Novel Therapeutic Targets for Managing Dyslipidemia
Sathiyakumar, V., Kapoor, K., Jones, S. R., Banach, M., Martin, S. S., & Toth, P. P. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.06.001 · Cited by 42 · see citing works
van Rooij, J., Arp, P., Broer, L., Verlouw, J., van Rooij, F. J. A., Kraaij, R., Uitterlinden, A. G., & Verkerk, A. J. M. H. (2020) · Genetics in Medicine · doi:10.1038/s41436-020-0900-8 · Cited by 41 · see citing works
NAT2 global landscape: Genetic diversity and acetylation statuses from a systematic review
Gutiérrez-Virgen, J. E., Piña‐Pozas, M., Hernández-Tobías, E. A., Taja‐Chayeb, L., López-González, M. D. L., Meraz‐Ríos, M. A., & Gómez, R. (2023) · PLoS ONE · doi:10.1371/journal.pone.0283726 · Cited by 44 · see citing works
Olkkonen, V. M., Sinisalo, J. P., & Jauhiainen, M. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.03.019 · Cited by 41 · see citing works
- Authors
- Saleheen, D., Natarajan, P., Armean, I. M., Zhao, W., Rasheed, A., Khetarpal, S. A., Won, H.-H., Karczewski, K. J., O’Donnell-Luria, A. H., Samocha, K. E., Weisburd, B., Gupta, N., Zaidi, M., Samuel, M., Imran, A., Abbas, S., Majeed, F., Ishaq, M., Akhtar, S., Trindade, K., Mucksavage, M., Qamar, N., Zaman, K. S., Yaqoob, Z., Saghir, T., Rizvi, S. N. H., Memon, A., Hayyat Mallick, N., Ishaq, M., Rasheed, S. Z., Memon, F.-U.-R., Mahmood, K., Ahmed, N., Do, R., Krauss, R. M., MacArthur, D. G., Gabriel, S., Lander, E. S., Daly, M. J., Frossard, P., Danesh, J., Rader, D. J., & Kathiresan, S.
- Affiliations
- Center for Non-Communicable Diseases (PK)
- Broad Institute (US)
- University of Pennsylvania (US)
- Samsung Medical Center (KR)
- Karachi Institute of Heart Diseases (PK)
- National Institute of Cardiovascular Diseases (PK)
- Civil Hospital Karachi (PK)
- Liaquat National Hospital (PK)
- Icahn School of Medicine at Mount Sinai (US)
- University of Cambridge (GB)
- Corresponding author
- Saleheen, Danish
- Kathiresan, Sekar
- ORCID
- Saleheen, Danish
- Natarajan, Pradeep
- Armean, Irina M.
- Zhao, Wei
- Khetarpal, Sumeet A.
- Won, Hong-Hee
- Karczewski, Konrad J.
- Samocha, Kaitlin E.
- Gupta, Namrata
- Zaidi, Mozzam
- Trindade, Kevin
- Qamar, Nadeem
- Saghir, Tahir
- Ishaq, Mohammad
- Rasheed, Syed Zahed
- Mahmood, Khalid
- Do, Ron
- Krauss, Ronald M.
- MacArthur, Daniel G.
- Gabriel, Stacey
- Lander, Eric S.
- Daly, Mark J.
- Danesh, John
- Rader, Daniel J.
- Kathiresan, Sekar
- Venue
- Nature
- Published
- 2017-04
- Volume
- 544
- Issue
- 7649
- Pages
- 235-239
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5600291
- OpenAlex
- W2605659507
- Cited by
- 340
- References
- 64
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 30 · 2023: 30 · 2022: 32 · 2021: 29 · 2020: 51 · 2019: 56 · 2018: 39 · 2017: 27 · 2016: 6
- FWCI
- 31.40
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Apollo
- Funders
- Pfizer
- Donovan Family Foundation
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0512-10165)
- British Heart Foundation (CH/12/2/29428, RG/13/13/30194, RG/16/4/32218, RG/08/014/24067)
- European Commission (279143, 279233)
- Fondation Leducq
- Cambridge University Hospitals (3819-1516-29, BRC 2012-2017, 3819-1617-25, 146281)
- National Institutes of Health
- Samsung
- Medical Research Council (MR/L003120/1, MR/M012816/1, MR/P013880/1)
- National Heart, Lung, and Blood Institute (R01HL107816)
- National Human Genome Research Institute (U54HG003067)
- National Institute of General Medical Sciences (R01GM104371)
- Fogarty International Center
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- loss-of-function mutations, consanguinity, homozygous mutation, gene function, phenotypic association, exome sequencing, PLA2G7, cardiometabolic traits, Pakistani population, reverse genetics, serum lipoproteins, interleukin-8, apolipoprotein B
- MeSH terms
- Cytochrome P450 Family 2, Consanguinity, Coronary Disease, Dietary Fats, DNA Mutational Analysis, Fasting, Female, Gene Frequency, Genes, Homozygote, Humans, Male, Middle Aged, Myocardial Infarction, Pakistan, Pedigree, Phenotype, Phosphoproteins, Triglycerides, Cohort Studies, Interleukin-8, Gene Deletion, Sodium-Hydrogen Exchangers, Postprandial Period, Neuregulins, RNA Splice Sites, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Apolipoprotein C-III, Genetic Association Studies, Reverse Genetics, Exome
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
