The DOI matches its Crossref record; 90 of the 90 references it cites were found in a registry or an index.
A genomic mutational constraint map using variation in 76,156 human genomes
Open accessPublished version of a preprint
Abstract
The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders 1-4, but attempts to assess constraint for non-protein-coding regions have proved more difficult. Here we aggregate, process and release a dataset of 76,156 human genomes from the Genome Aggregation Database (gnomAD)-the largest public open-access human genome allele frequency reference dataset-and use it to build a genomic constraint map for the whole genome (genomic non-coding constraint of haploinsufficient variation (Gnocchi)). We present a refined mutational model that incorporates local sequence context and regional genomic features to detect depletions of variation. As expected, the average constraint for protein-coding sequences is stronger than that for non-coding regions. Within the non-coding genome, constrained regions are enriched for known regulatory elements and variants that are implicated in complex human diseases and traits, facilitating the triangulation of biological annotation, disease association and natural selection to non-coding DNA analysis. More constrained regulatory elements tend to regulate more constrained protein-coding genes, which in turn suggests that non-coding constraint can aid the identification of constrained genes that are as yet unrecognized by current gene constraint metrics. We demonstrate that this genome-wide constraint map improves the identification and interpretation of functional human genetic variation.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Neutral, non-disease causing SALL1 variants (predicted loss-of-function, pLoF) were obtained from the gnomAD 48 database (v4.1.0, https://gnomad.broadinstitute.org/), with the following selection criteria: >2 cases found for each specific variant, no flag associated with dubious sequencing quality or possible pathogenicity.”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [48]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“we found that SALL1 is depleted of similar mutations in the healthy population, as a gnomAD 48 database (v4.1.0, https://gnomad.broadinstitute.org/) search identified only three variants, all at the C-terminus of the protein after SALL1 ZFC4”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [48]
The cited source says what the claim attributes to it.
In the citing paper
“We note that there are many SNPs common (>5%) in these Polynesian sequences that are entirely absent from gnomAD (Fig. 1B) (6).”
From Message in a bottleneck: Nested founder effects from French Polynesia to Rapa Nui and Hawaiʻi (2026) · cites this paper as [6]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For inclusion on these population-specific screening panels, the ACMG recommends a carrier frequency of >1/200 (5, 6).”
From Message in a bottleneck: Nested founder effects from French Polynesia to Rapa Nui and Hawaiʻi (2026) · cites this paper as [6]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247
Self-citationpROC: an open-source package for R and S+ to analyze and compare ROC curves
Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.-C., & Müller, M. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-77 · Cited by 13,697
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
Self-citationThe mutational constraint spectrum quantified from variation in 141,456 humans
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., et al. (2020) · Nature · doi:10.1038/s41586-020-2308-7 · Cited by 9,434
Self-citationIntegrative 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
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
GENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585
ClinVar: improving access to variant interpretations and supporting evidence
Landrum, M. J., Lee, J. M., Benson, M., Brown, G. R., Chao, C., Chitipiralla, S., Gu, B., Hart, J., Hoffman, D., Jang, W., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1153 · Cited by 4,196
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Cited by
Sorted by citations
Items 901–1,000 of 1,003
Actionability of Genetic Variants in Diabetes: Core Aspects and Applied Examples
Yvonnet, S., Reim, P. K., & Thuesen, A. C. B. (2025) · Diabetes Spectrum · doi:10.2337/ds24-0081 · Cited by 1
“Evidence of pathogenicity is provided through the assessment of a variant ’ s frequency in population variation databases such as GnomAD (48), prevalence among patients, predictive and computational evidence of the biological consequence of a variant, and functional characterization.”
Monitoring the rate and variability of somatic genomic alterations using long-read sequencing
Chen, X., Ligumsky, H., Ambrose, C., Sibrian, D., Tran, B. H., Arif, D., Castellanos, O. O., Kessner, D., Luo, H., Ubale, M., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-01690-z · Cited by 1
Impact of CHEK2 germline variants on haematological malignancy risk and outcomes of allogeneic HSCT
Lahtinen, A., Karu, M., Koski, J., Ritari, J., Hyvärinen, K., Koskela, S., Nihtilä, J., Partanen, J., Vettenranta, K. K., Koskenvuo, M., et al. (2025) · British Journal of Haematology · doi:10.1111/bjh.20196 · Cited by 1
“14 The ascending role of CHEK2 variants in HM predisposition and the lack of reports on their impact on the outcomes of HSCTs prompted us to perform this study.”
Rosen, N., Holling, T., Junod, I., Alawi, M., Ossama, H. M., ElGhandour, R. K., Abdalla, E. M., & Kutsche, K. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.05.036 · Cited by 1
Bolcato, M., Romito, G., Häfliger, I. M., Gentile, A., Drögemüller, C., & Jacinto, J. G. P. (2025) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.70144 · Cited by 1
“Large data from human genome sequencing studies presented in the Genome Aggregation Database (gnomAD) showed that the probability of loss- of-function intolerance score for WDR33 was 1, meaning that this gene falls into the class of loss- of-function haploinsufficient genes [27].”
Nguyen, T., Trần, V. K., Ngoc-Nguyen, L., Huy, N. V., Tran, T. H., Phuong, L. T., Nguyen, P. L., Nguyen, T. T., Trang, T. T. Q., Huong, D. T., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13071625 · Cited by 1
“1.0) [34 ], dbSNP157 [35], and ClinVar [36].”
InfluentialFasano, C., Buonadonna, A. L., Forte, G., Signorile, M. L., Grossi, V., Marco, K. D., Sanese, P., Manghisi, A., Tutino, N. M., Armentano, R., et al. (2025) · Cancers · doi:10.3390/cancers17142308 · Cited by 2
“1 dataset (https://gnomad.broadinstitute.org/ news/2024-04-gnomad-v4-1/; accessed on 24 June 2025) [18].”
InfluentialCaMutQC: An R package for integrative quality control and filtration of cancer somatic mutations
Wang, X., Jiang, T., Shen, A., Chen, Y., Zhou, Y., Liu, J., Zhao, S., Chen, S., Ren, J. M., & Zhao, Q. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.07.011 · Cited by 2
“By default, it re-tains CAMs that are either absent from germline variant databases such as ExAC [21] and ESP6500 [22] or present but with VAF below 0.01. gnomAD [23]-based filtration is also supported.”
InfluentialSelf-citationLee, G., Kim, S. J., Kwon, H. C., Sub, Y., Gee, H. Y., & Lee, S. (2025) · Kidney International Reports · doi:10.1016/j.ekir.2025.07.031 · Cited by 1
Stratifying GAP Stages by MUC5B rs35705950 T-Allele Carriage Refines Survival Prediction in IPF
van der Vis, J. J., Prasse, A., Renzoni, E. A., Stock, C. J. W., Maher, T. M., Bonella, F., Borie, R., Crestani, B., Wuyts, W. A., Molyneaux, P. L., et al. (2025) · Lung · doi:10.1007/s00408-025-00837-z · Cited by 1
Xiang, K., & Bartel, D. P. (2025) · Nature Communications · doi:10.1038/s41467-025-62171-5 · Cited by 1
“The code available in the GitHub repository uses the default initializer and dropout, which is not a very fortunate choice if one does not want SELU to lose its self-normalizing properties.”
Brunello, F. G., Erra, L., Nicola, J., & Martí, M. A. (2025) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1012829 · Cited by 1
Stafie, S. T., Lindquist, M., Kusher-Lenhoff, S., Nakamichi, K., & Mustafi, D. (2025) · Ophthalmic Genetics · doi:10.1080/13816810.2025.2544639 · Cited by 1
“The most widely used database for gene variant interpretation is the Genome Aggregation Database (gnomAD) (6, 7).”
Wang, Y., Meng, K., Chen, H., Jin, X., Yang, G., Ma, G., Cheng, Y., Zhao, C., Zheng, C., Xie, M., et al. (2025) · BMC Ophthalmology · doi:10.1186/s12886-025-04201-w · Cited by 1
“Additional manifestations encompass ocular anomalies and neutropenia [1].”
Self-citationPrediction of Human Pathogenic Start Loss Variants Based on Multi-channel Features
Liu, J., Wang, L., Su, Y., Ye, B., & Xia, J. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c01258 · Cited by 1
Self-citationFateen, E., Nosier, S. S., Abdelaziz, N., Radwan, A. M., & Mohammed, E. E. A. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03971-2 · Cited by 1
Latifi, A., & Yousefian, S. (2025) · eJHaem · doi:10.1002/jha2.70136 · Cited by 1
“While this variant has been identified once in heterozygous form in the IGSR database (1000 Genomes), it is absent from ClinVar and Genome Aggregation Database (gnomAD) [5], and has not previously been associated with a clinical phenotype.”
Clonal Hematopoiesis and Cardiovascular Events in Patients with ESKD on Hemodialysis
Englisch, C., Königsbrügge, O., Vostatek, R., Säemann, M. D., Schmaldienst, S., Pabinger, I., Jäger, R., & Ay, C. (2025) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.0000000833 · Cited by 1
Haffener, P. E., Al‐Riyami, A. Z., Al‐Zadjali, S., Al‐Rawahi, M., Hosni, S. A., Al‐Marhoobi, A., Sheriyani, A. A., & Leffler, E. M. (2025) · Transfusion · doi:10.1111/trf.18401 · Cited by 1
Kurva, J., Bhat, N., Ghosh, A., Tawade, H., Cherian, S., & Shettigar, S. K. G. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10996-0 · Cited by 1
Shen, Q., Wang, Z., Lin, J., Li, L., Zhang, S., Wang, S., & Li, C. (2025) · International Journal of Legal Medicine · doi:10.1007/s00414-025-03575-2 · Cited by 1
“The loss-of-function observed/ expected upper bound fraction (LOEUF), probability of being loss-of-function intolerant (pLI), and the deviation of observed variant counts from the expected variant counts (Z scores) were based on gnomAD v4 datasets [ 37].”
Mouse variants in Taf1c result in reduced survival to birth
Watts, J. L., Willeke, L., & Stottmann, R. W. (2025) · Developmental Biology · doi:10.1016/j.ydbio.2025.09.011 · Cited by 1
Jury, J., Besnard, T., Deb, W., Toutain, A., Gueguen, P., Bruel, A., Bouman, A., Veenma, D. C. M., Barakat, T. S., Souto, L. D., et al. (2025) · Journal of Medical Genetics · doi:10.1136/jmg-2024-110471 · Cited by 1
Ollendorff, M. K., Dinesen, S. B., Ahlgreen, O. A., Madsen, P., Mølgaard, S., Dalby, A., Gustafsen, C., Olsen, D., Duan, J., Vilstrup, J., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03242-3 · Cited by 2
“1D) and the R702W variant is reported 39 times in GnomAD [29], rendering an allele frequency of 0.000025.”
InfluentialA rare autoinflammatory syndrome associated with a C2orf69 frameshift mutation: a case report
Türkmen, Ş., Yarar, M. H., Tosun, İ., Bozkurt, H. B., & Sözeri, B. (2025) · Immunologic Research · doi:10.1007/s12026-025-09693-8 · Cited by 1
Significance of incidental copy number variants in the Duchenne muscular dystrophy gene
Ginjaar, I. B., Kriek, M., Hoffer, M. J. V., Oegema, R., van Binsbergen, E., Diderich, K. E. M., van Zutven, L. J. C. M., Duijkers, F. A. M., Knegt, A. C., Erasmus, C. E., et al. (2025) · Neuromuscular Disorders · doi:10.1016/j.nmd.2025.106219 · Cited by 1
Radenković, L., Pantović-Stefanović, M., Brajušković, G. N., Ivković, M., Pavicevic, D. S., & Pešović, J. (2025) · Genes · doi:10.3390/genes16101141 · Cited by 1
“; Table S4: Aligned Rank Transform (ART) ANOVA results for all model-derived features across diagnostic and suicide attempt groups [29,51–53].”
Bao, Y., Soh, S., Li, J., Zuo, Z. C., Ferdous, S., Qian, X., Li, J., Lu, J., Cheng, X., Matynia, A., et al. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110677 · Cited by 2
De Novo Variants in PPFIA2 in Individuals With Neurodevelopmental Disorders
Brunet, T., Zech, M., Schatz, U. A., Adamovičová, M., Wagner, M., Graf, E., Berutti, R., Weigand, H., Jech, R., Meitinger, T., et al. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.64255 · Cited by 1
A de novo frameshift variant in the candidate RBM15 in a proband with congenital mirror movements
Harms, F. L., Kortüm, F., Alawi, M., Staudt, M., & Kutsche, K. (2025) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2025.100528 · Cited by 1
Padilla, L., del Val, C., Neidre, D. B., Kokenge, A. S., Martinez, J. E., Teixeira, A. L., Zwir, I. J. S., & de Erausquin, G. A. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1631536 · Cited by 1
“1.2 ( Chen et al., 2024) and ClinVar (Landrum et al., 2014) databases.”
InfluentialWagner, J. T., Welle, J. T., Beckett, I. L., Emery, K. R., Cosgrove, B. A., Olszewski, K., Wagner, N., Bower, T. C., Yuan, L. C., Shull, E. M., et al. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1669085 · Cited by 1
Li, M., & Liang, C. (2025) · Genes · doi:10.3390/genes16101202 · Cited by 1
The APOE ε4 allele affects the survival of patients with Parkinson's disease independent of dementia
Wang, Z., Lu, L., Xu, Q., Pan, H., Wang, Y., Qin, L., Huang, Y., Dai, Y., Zhang, S., Zhou, Q., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07169-9 · Cited by 1
Carbonic anhydrase VA deficiency due to a novel CA5A variant
Keehan, L. A., Null, E., Chilakamarri, L., Carter, C., Lee, C. U., Enns, G. M., & Matalon, D. R. (2025) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2025.101259 · Cited by 1
“1.0) with no homozygotes [12].”
InfluentialZhu, H., Zeng, Q., Leach, N. T., Letovsky, S. I., Rafalko, J. M., Huang, B., Bhojanna, S. M., Iyer, L. K., Kenyon, A. L., & Heim, R. A. (2025) · BMJ connections. · doi:10.1136/bmjccgg-2025-000026 · Cited by 1
Functional Characterization of a Novel GPC3 Missense Variant in Simpson–Golabi–Behmel Syndrome
Zhao, T., Allan, K., Taylor, J. P., Thorburn, D. R., White, S. M., Tan, T. Y., Christodoulou, J., Tan, N. B., & Stroud, D. A. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.64287 · Cited by 1
Borovikov, A. O., Davydenko, K., Murtazina, A. F., Sharkov, A. A., Kanivets, I. V., Filatova, A. Y., & Skoblov, M. Y. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1670299 · Cited by 1
Franco, A. L. M. M., Antunes, D., Gomes, A. C. R. M., Dias, B., Cintra, H. P. L., Guimarães, A. C. R., de Carvalho, E. F., Vargas, F. R., & de Carvalho, F. M. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.10.013 · Cited by 1
“Population allele frequencies were compared using - data from the 1000 Genomes Project [17], AbraOM [18], and gno mAD [19].”
Functional analysis of FH variants of uncertain significance using Caenorhabditis elegans model
Ferris, S., Menéndez‐Perdomo, I. M., & Tarailo‐Graovac, M. (2025) · Genetics in Medicine Open · doi:10.1016/j.gimo.2025.103469 · Cited by 2
“38 and likely pathogenic effect prediction from the in silico tool AlphaMissense 39 (Supplemental Table 5) further point toward each of these 5 alleles having deleterious effects.”
Kumari, B., Arya, S., Khare, R., Garg, I., Prince, Joshi, R. K., Kumar, R., & Srivastava, S. (2025) · Gene Reports · doi:10.1016/j.genrep.2025.102379 · Cited by 1
Koch, R. L., Fares, A. H., Cocanougher, B., Lim, J., Schreuder, A. B., Derks, T. G. J., Grünert, S. C., Sharma, R., Jones, K. A., & Kishnani, P. S. (2025) · npj Genomic Medicine · doi:10.1038/s41525-025-00527-y · Cited by 1
Liang, Y. Y., Ormazábal‐Toledo, R., Srinivasan, H., Malci, A., Acevedo, W., Thomas, U., Cohen, J. S., Rahner, N., Luppe, J., Vera, G., et al. (2026) · Genome Medicine · doi:10.1186/s13073-026-01699-7 · Cited by 1
“1.1 dataset served as the control population [36].”
InfluentialSequence context and methylation interact to shape germline mutation rate variation at CpG sites
Chandra, S., & Gao, Z. (2026) · PLoS Genetics · doi:10.1371/journal.pgen.1011957 · Cited by 1
“Quantifying and accounting for this mutation rate variation is important for making inferences about natural selection [2] and identifying functional coding [3–6] and non-coding regions [7].”
Álvarez-Arce, A., Fritzmann, G. E., Burnham, H. V., Araujo, K., Peña, A., Wittenkeller, L. M., Cizauskas, H. E., & Barefield, D. Y. (2025) · The Journal of General Physiology · doi:10.1085/jgp.202413630 · Cited by 1
Genomic variation of human microRNAs and its association with functional features
Cihan, M., Andrade-Navarro, M. A., & Morett, E. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05936-x · Cited by 2
“By leveraging the expanded gnomAD v4 dataset [ 13], which provides substantially greater cov - erage than gnomAD v3 (a fivefold increase in WGS and a sixfold increase in WES datasets), we identified 55,796 variants in precursor and mature miRNAs.”
InfluentialLeveraging a Genetic Proxy to Investigate the Effects of Lifelong Cardiac Sodium Channel Blockade
Wanner, J. S., Krafft, M., Niiranen, T., Zimmerman, D. S., FinnGen, Ellinor, P. T., Nadkarni, G. N., Jurgens, S. J., Rämö, J. T., & Heyne, H. (2025) · Circulation · doi:10.1161/circulationaha.125.075057 · Cited by 1
Self-citationAnderson, C. L., Munuwar, S., Walters, J., McWilliams, S. F., Melnick, M., Langer, E. R., Bereslavskyy, I., Milaitis, M. R., Reilly, L., & Eckhardt, L. L. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110985 · Cited by 1
Pathogenic POLE-Mutated Endometrial Carcinomas With a Nonultramutated Genome
Srikumar, S., Evans, N., Tjota, M. Y., Alikhan, M. B., Kaur, A., Sabatini, L. M., Miller, N., Bouma, M., Maniar, K. P., & Parilla, M. (2025) · Modern Pathology · doi:10.1016/j.modpat.2025.100946 · Cited by 1
Medically actionable DNA variants have a prevalence of 5 % in the Cyprus genetic landscape
Fanidis, D., Moutsouri, E., Malatras, A., Shuldiner, A. R., Alkelai, A., Polydorou, C., Papagregoriou, G., & Deltas, C. C. (2025) · Genomics · doi:10.1016/j.ygeno.2025.111169 · Cited by 1
Truncating Titin and Lamin A/C Variants in Anthracycline-Induced Cardiomyopathy
Advani, P. P., McPherson, A. D., Reddy, J. S., Schneider, J. W., Baheti, S., Nguyen, T. D., Ray, J. C., & Norton, N. (2025) · JACC Advances · doi:10.1016/j.jacadv.2025.102431 · Cited by 1
Xu, K., Zhang, B., Zhao, S., Zhang, Y., Wu, N., Shen, M., & Zeng, X. (2025) · Journal of Clinical Immunology · doi:10.1007/s10875-025-01971-2 · Cited by 1
“Variant density was defined as the number of observed nonpathogenic vari - ants in the gnomAD database divided by the length of the region and was used to estimate regional tolerance in the 5’ UTR [23].”
WES-Based Screening of a Swedish Patient Series with Parkinson’s Disease
Kafantari, E., Brolin, K. A., Wallenius, J., Swanberg, M., & Puschmann, A. (2025) · Genes · doi:10.3390/genes16121482 · Cited by 2
“A filtering strategy was followed where variants with a minor allele frequency (MAF) 0.02 in gnomAD, non-Finnish European exomes and genomes [11], and a genotype quality of more than 20 were selected.”
InfluentialA practical framework for predicting splicing single nucleotide variants in exome sequencing
Utsuno, Y., Hamanaka, K., Sakamoto, M., Tsuchida, N., Uchiyama, Y., Koshimizu, E., Fujita, A., Miyatake, S., Mizuguchi, T., & Matsumoto, N. (2025) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaf180 · Cited by 1
“The first list included genes with an En-hancer Gnocchi score of ≥ 4 [ 13 ], signifying strong regulatory potential.”
B-cell lymphocytosis and reprogramming due to biallelic CARD11 mutations
Bhattad, S., Gil, H. M., Ruchinskas, A., Stinson, J. R., Boone, A. T. S., Mohite, R., Janardhanan, J., Singh, N., Mariskanish, C., Choi, J. M., et al. (2025) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2025.12.991 · Cited by 2
Raraigh, K. S., Balcom, J. R., & Langfelder-Schwind, E. (2025) · Journal of Genetic Counseling · doi:10.1002/jgc4.70151 · Cited by 1
“Population data (Chen et al., 2024) [c.443T > C]), while 5T;TG12 has an allele frequency of 3.9% in the Ashkenazi Jewish population—well above the previously defined 1% polymorphism threshold (Brookes, 1999).”
InfluentialDe novo variants in KDM2A cause a syndromic neurodevelopmental disorder
Anderson, E. N., Drukewitz, S., Kour, S., Chimata, A. V., Rajan, D. S., Schönnagel, S., Stals, K. L., Donnelly, D., O’Sullivan, S. S., Mantovani, J. F., et al. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.12.004 · Cited by 5
Cloud computing in population-scale genomics: Strategies, challenges, and future directions
Kim, S., Kim, T., Lee, S., Seo, H. K., Kang, J., Kang, D., Jeon, I., & Choi, J. (2025) · Journal of genetic medicine · doi:10.5734/jgm.2025.22.2.37 · Cited by 2
Forte, G., Fasano, C., Iacoviello, M., Grossi, V., Signorile, M. L., Marco, K. D., Sanese, P., Buonadonna, A. L., Manghisi, A., Tutino, N. M., et al. (2026) · Biomedicines · doi:10.3390/biomedicines14010087 · Cited by 1
“1 dataset (https://gnomad.broadinstitute.org/news/2024-04-gnomad-v4-1/; accessed on 10 September 2025) [16].”
Qadir, A., Shah, I. A., Mir, M. R., Sofi, J. A., Radha, V., Mohan, V., Ganie, S. A., & Ganie, M. A. (2026) · Clinical Endocrinology · doi:10.1111/cen.70091 · Cited by 1
“The variant has not been reported in Indigenome [ 25], 1000 Genomes, or the gnomAD database [26].”
MobiCT: a UMI-based circulating tumor DNA analysis pipeline
Cabello‐Aguilar, S., Goethem, C. V., Delmas, J.-C., Bourbia, O., Senal, R., Cossée, M., Ardouin, O., Solassol, J., & Vendrell, J. A. (2025) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaf212 · Cited by 1
“Finally, variants with an allele frequency > 1% in the gnomAD database [ 13 ] are excluded.”
Starosta, R. T., He, M., Gracie, S., Kierstein, J., Thiel, C., Himmelreich, N., Liu, Y., Zhang, W., Edmondson, A. C., Meeks, N. J. L., et al. (2026) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2026.109727 · Cited by 1
Genetic landscape of pediatric acute myeloid leukemia in Taiwan
Cheng, Z., Yu, S., Yu, C.-H., Chang, T., Chang, Y.-H., Jou, S., Lü, M.-Y., Lin, K.-H., Hsiu-Hao, C., Chou, S.-W., et al. (2026) · Scientific Reports · doi:10.1038/s41598-025-34152-7 · Cited by 1
Werwath, K. E., Lawn, R. B., Salem, M., Li, T., Mitchell, B. L., Shen, H., Gordon, S. D., Kung, B., Stafford, C., Vemuri, M., et al. (2026) · Communications Medicine · doi:10.1038/s43856-025-01305-8 · Cited by 1
Self-citationBreast cancers arising in high mammographic density tissue harbor tumor-promoting immune profiles
Cheasley, D. A., Ruppert, M., Devereux, L., Jayawardana, M., Zhao, Q., Nickson, C., Pereira, M., Byrne, D. J., Fox, S. B., CAMPBELL, I. G., et al. (2026) · npj Breast Cancer · doi:10.1038/s41523-025-00884-y · Cited by 1
“…fi c sequencing depth >10; tumour alternate allele fraction ≥ 25% and ≤ 75%; germline alternate allele fraction <10%; exclusion of variants documented as known germline polymorphisms in the Single Nucleotide Polymorphism Database 43 ; and a global allele frequency <0.0005 in gnomAD v3 44 .”
InfluentialKeerthipriya, M. S., Kotambail, A., Deekshitha, M., Mahima, R., Ramyashree, M. B., Rao, B. M., Biswas, P., Baskar, D., Balaji, P., Mehta, M., et al. (2026) · Journal of Neurology · doi:10.1007/s00415-025-13612-0 · Cited by 1
Turan, İ., Atar, M., Eltan, M., Anık, A., Bitkin, E. Ç., Doğruel, D., Çay, M., Bozdoğan, S. T., Döneray, H., Kotan, D., et al. (2026) · Calcified Tissue International · doi:10.1007/s00223-025-01462-x · Cited by 1
Rare heterozygous de novo variants in RAPGEF2 are associated with a neurodevelopmental disorder
Bereshneh, A. H., Wilson, K. A., Pan, X., Hannan, S. B., Cooper, M. A., Diaz, J., Leon, E. L., Moses, T. M., Azamian, M. S., Scott, D. A., et al. (2026) · Genetics in Medicine · doi:10.1016/j.gim.2026.101685 · Cited by 1
Khanshour, A. M., Haddad, C., Meregini, S., Zamudio, M., Arneson, A., Parrish, C. P., Bird, J. A., & SoRelle, J. A. (2026) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2026.01.001 · Cited by 1
Rothschild, H., & Hillman, R. T. (2026) · Gynecologic Oncology · doi:10.1016/j.ygyno.2026.01.008 · Cited by 1
MDGA2 homozygous loss-of-function variants cause developmental and epileptic encephalopathy
Morsy, H., Kim, H., Jang, G., Zaki, M. S., Severino, M., Abdelrazek, I. M., Hussien, H., Self, E., Albaradie, R., Bakur, K., et al. (2026) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.12.015 · Cited by 2
O'Brien, J. A., Ramaker, R. C., Moyer, A. N., Strickler, J. H., Tong, B. C., Ramaker, M. E., Shah, S. H., Alder, L., Stinchcombe, T. E., & Clarke, J. (2026) · JCO Precision Oncology · doi:10.1200/po-25-00678 · Cited by 1
Self-citationFussell, D., Leber, M., Vandewege, M. W., Stern, J. A., Meurs, K. M., Armwood, A. R., & Herrmann, I. (2026) · Journal of Veterinary Diagnostic Investigation · doi:10.1177/10406387251414540 · Cited by 1
“5 Although we cannot fully rule out the possibility that the feline PLEC missense variant is causal or at least additive, circum-stantial evidence suggests that the amino acid position can vary, and the V/A missense variant is likely benign.”
Buco, P. A. V., Hoque, A., Castillo‐Tandazo, W., Chalk, A. M., Smeets, M. F. M. A., & Walkley, C. R. (2026) · BMC Genomics · doi:10.1186/s12864-026-12574-5 · Cited by 1
“Although the precise cause and time of embryonic lethality remains undetermined, this is consistent with human data showing an intolerance to KLHDC3 loss-of-function variants (gnomAD browser) [60, 61].”
Gain-of-Function Variant TRPC6 A404V Is Associated With Doxorubicin-Related Cardiomyopathy
Wu, Y., SUN, X., Wang, R. X., Reddy, J. S., Lee, H.-C., Norton, N., & Lu, T. (2026) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.125.005334 · Cited by 1
Coşar, Ö. S., Kayhan, G., Akyol, G., & Dalgıç, B. (2026) · Pediatric and Developmental Pathology · doi:10.1177/10935266261417523 · Cited by 1
Clinical and genetic features of idiopathic pulmonary fibrosis in a Korean cohort
Kim, C., Kim, S. Y., Woo, A., Shin, J. H., SUNG, M., & Park, M. S. (2026) · Respiratory Research · doi:10.1186/s12931-026-03504-w · Cited by 1
“Allele frequencies were determined for the entire cohort and compared with multiple reference databases, including gnomAD [26], 1000 Genomes Project [27], Korean Reference Genome Database (KRGDB) [28], TopMed [29], and East Asian-specific databases [26, 27, 29].”
Nagao, G., Namkoong, H., Tanaka, H., Asakura, T., Hara, A., Fukunaga, N., Kaji, M., Azekawa, S., Nakagawara, K., Morita, A., et al. (2026) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2025-003683 · Cited by 1
Disruption of meiotic double-strand break dynamics provokes germline human infertility in both sexes
Okutman, Ö., Sassi, A., Şalvarcı, A., Lambert, S. M., Brachet, C., Peyrassol, X., Lang, C., Alptekin, D. S., Özen, R. S., Muller, J., et al. (2026) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-026-03820-6 · Cited by 2
Smart, S. E., Fenner, E., Rhys, H., Wells, A., Fender, K., Bresner, C., Trauzzi, G., Willcocks, I. R., Legge, S. E., Pardiñas, A. F., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0340584 · Cited by 1
“We will use metrics such as gnomAD’s loss-of-function observed/expected upper bound fraction (LOUEF) [98] to define constrained genes, but will be alert to methodological developments in this area.”
Self-citationTosi, M., Favero, F., Zuccalà, M., Visha, E., Caushi, F., Barizzone, N., Pomella, N., Follia, L., Corrado, L., Corà, D., et al. (2026) · Neurological Sciences · doi:10.1007/s10072-026-08813-y · Cited by 1
Varga, L., Borecká, S., Škopková, M., Rambani, V., Sklenar, M., Cipkova, K., Kickova, T., Ugorová, D., Kabátová, Z., Stanik, J., et al. (2026) · Ear and Hearing · doi:10.1097/aud.0000000000001780 · Cited by 1
“While our data do not provide estimated variant prevalence for the general population in Slovakia, this is estimated to be 1:10,000 according to the GnomAD v.4.1.0 population database (Chen et al. 2024).”
InfluentialRare KDM4C variants and reduced expression underlie epigenetic dysregulation in rheumatoid arthritis
Öner, D. A., Toktaş, H., Dündar, Ü., Adar, S., & Eyvaz, N. (2026) · Immunologic Research · doi:10.1007/s12026-026-09751-9 · Cited by 1
“Variant interpretation was performed according to ACMG/AMP guidelines [7, 23, 39, 44].”
Carter, M. A., & Scully, M. (2026) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2026.01.022 · Cited by 1
Multiple-testing corrections in case-control studies using identity-by-descent segments
Temple, S. D., Chapman, N. H., Choi, S. H., DeStefano, A. L., Thornton, T. A., Wijsman, E. M., & Blue, E. (2026) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2026.01.013 · Cited by 2
Inherited burden for disease predisposition in diverse populations
Kayaalp, B., Kars, M. E., Itan, Y., Basak, A. N., Casanova, J., & Özçelık, T. (2026) · npj Genomic Medicine · doi:10.1038/s41525-026-00552-5 · Cited by 2
“Gene Constraint Metrics pLI, LOEUF, and missense and synonymous Z scores were downloaded from https://gnomad.broadinstitute.org/data#v4-constraint for gnomAD version 4 21 .”
Radjasandirane, R., Cretin, G., Diharce, J., de Brevern, A. G., & Gelly, J. (2026) · Artificial Intelligence in the Life Sciences · doi:10.1016/j.ailsci.2026.100165 · Cited by 1
Variants in NR6A1 as a cause for congenital renal, vertebral and uterine anomalies
Jacquinet, A., Flasse, L. C., Dohet, M., Vanhaeren, R., Pendeville, H., Saunders, C. A., Lehman, A., Pienkowski, C., Morcel, K., Guerrier, D., et al. (2026) · Human Genetics · doi:10.1007/s00439-025-02806-1 · Cited by 3
Johansson, P. A., Palmer, J. M., Brooks, K. M., Chan, H. H., Pritchard, A., Wilson, D., Martin, L., Guitera, P., & Hayward, N. (2026) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2026.02.012 · Cited by 1
Tibbe, D., Holling, T., Spohn, M., Alawi, M., Nampoothiri, S., & Kutsche, K. (2026) · Human Genetics · doi:10.1007/s00439-025-02813-2 · Cited by 1
Comprehensive genetic rescreening improves diagnostic yield in congenital hyperinsulinism
Männistö, J. M. E., Houghton, J., Bennett, J. J., Keskinen, P., Tuomilehto, J., Ruuskanen, H., Viikari, L. A., Jokiniitty, A., Lähde, J., Raivo, J., et al. (2026) · Journal of the Endocrine Society · doi:10.1210/jendso/bvag047 · Cited by 1
“Alternatively, given the relatively high allele frequency of this founder variant ( ∼ 1:300 individuals among Finnish Europeans in gnomAD v4, and up to 3.5% carrier frequency in certain areas of Finland) [30, 41], the variant may represent an incidental finding unrelated to HI in these patients.”
InfluentialMarin, V. T. W., Lannes, H., Dumont, V., Thévenon, J., Baux, D., Roux, A., Lasseaux, E., Pennamen, P., & Lebreton, L. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-026-02068-z · Cited by 1
“1 and v4 database [8] : pLi (probability of being loss-of-function intolerant), LOEUF (loss-of-function observed/expected upper bound fraction), MOEUF (missense observed/expected upper bound fraction) and missense Z-Score.”
Exploring the hereditary genetic mutational landscape of breast and ovarian cancer in Estonia
Tooming, M., Toome, K., Rekker, K., Roht, L., Laidre, P., Fjodorova, O., Roomere, H., Murumets, Ü., Šamarina, U., Pajusalu, S., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-43459-y · Cited by 1
“Its rarity in other populations per gnomAD 20 , suggest a possible Estonian founder effect.”
Canavati, C., Oppebøen, M., Verma, R., Misceo, D., Frengen, E., Salvador, C. L., Martínez‐Gil, N., Cueto-González, A. M., Strømme, P., Marthinsen, P. B., et al. (2026) · Genetics in Medicine · doi:10.1016/j.gim.2026.102553 · Cited by 1
De novo TANC2 stop‐loss variant associated with developmental impairment and drug‐resistant epilepsy
Hintermayer, M. A., & Myers, K. A. (2026) · Epileptic Disorders · doi:10.1002/epd2.70219 · Cited by 1
Johnson, M. B., Russ‐Silsby, J., Blair, P. A., Govier, M., Bonfield, G., Domingo‐Vila, C., Wakeling, M. N., Oram, R. A., Flanagan, S. E., Tree, T. I. M., et al. (2026) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2026.02.017 · Cited by 1
The selective dynamics of interruptions at short tandem repeats
Goldberg, M. E., Dashnow, H., Harris, K., & Quinlan, A. R. (2026) · Genetics · doi:10.1093/genetics/iyag080 · Cited by 2
“Many meth-ods identify constrained high-complexity genomic regions as those depleted for SNP variation under a neutral model of their mutagenesis (Lek et al. 2016; Havrilla et al. 2019; Karczewski et al. 2020; Chen et al. 2024a).”
Cancer genome standards for long-read sequencing using cancer cell line mixtures
Zhang, J., Wong, H. Y., Liu, L., Koufariotis, L. T., Wood, S., Fitzpatrick, N., Quiatchon, J., Collins, P., Pearson, J. V., & Waddell, N. (2026) · GigaScience · doi:10.1093/gigascience/giag037
“We estimate the germline leakage rate by quantifying somatic calls with a maximum population frequency above 0.1 in gnomAD (version 4.1) [ 42 ].”
InfluentialMitsuhashi, N., Fujiwara, T., & Yamaguchi, A. (2026) · Human Genome Variation · doi:10.1038/s41439-026-00344-4 · Cited by 1
Acharya, A., Järvelä, I. E., Hernandez, A., Rajendran, Y., Bharadwaj, T., Goodloe, D. H., Hiatt, S. M., Morrison, J., Wheeler, P. G., Hunter, J. M., et al. (2026) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2026.100613 · Cited by 1
Metadata
- Authors
- Chen, S., Francioli, L. C., Goodrich, J. K., Collins, R. L., Kanai, M., Wang, Q., Alföldi, J., Watts, N. A., Vittal, C., Gauthier, L. D., Poterba, T., Wilson, M. W., Tarasova, Y., Phu, W., Grant, R., Yohannes, M. T., Koenig, Z., Farjoun, Y., Banks, E., Donnelly, S., Gabriel, S., Gupta, N., Ferriera, S., Tolonen, C., Novod, S., Bergelson, L., Roazen, D., Ruano-Rubio, V., Covarrubias, M., Llanwarne, C., Petrillo, N., Wade, G., Jeandet, T., Munshi, R., Tibbetts, K., Genome Aggregation Database Consortium, Abreu, M., Aguilar Salinas, C. A., Ahmad, T., Albert, C. M., Ardissino, D., Armean, I. M., Atkinson, E. G., Atzmon, G., Barnard, J., Baxter, S. M., Beaugerie, L., Benjamin, E. J., Benjamin, D., Boehnke, M., Bonnycastle, L. L., Bottinger, E. P., Bowden, D. W., Bown, M. J., Brand, H., Brant, S., Brookings, T., Bryant, S., Calvo, S. E., Campos, H., Chambers, J. C., Chan, J. C., Chao, K. R., Chapman, S., Chasman, D. I., Chisholm, R., Cho, J., Chowdhury, R., Chung, M. K., Chung, W. K., Cibulskis, K., Cohen, B., Connolly, K. M., Correa, A., Cummings, B. B., Dabelea, D., Danesh, J., Darbar, D., Darnowsky, P., Denny, J., Duggirala, R., Dupuis, J., Ellinor, P. T., Elosua, R., Emery, J., England, E., Erdmann, J., Esko, T., Evangelista, E., Fatkin, D., Florez, J., Franke, A., Fu, J., Färkkilä, M., Garimella, K., Gentry, J., Getz, G., Glahn, D. C., Glaser, B., Glatt, S. J., Goldstein, D., Gonzalez, C., Groop, L., Gudmundsson, S., Haessly, A., Haiman, C., Hall, I., Hanis, C. L., Harms, M., Hiltunen, M., Holi, M. M., Hultman, C. M., Jalas, C., Kallela, M., Kaplan, D., Kaprio, J., Kathiresan, S., Kenny, E. E., Kim, B.-J., Kim, Y. J., King, D., Kirov, G., Kooner, J., Koskinen, S., Krumholz, H. M., Kugathasan, S., Kwak, S. H., Laakso, M., Lake, N., Langsford, T., Laricchia, K. M., Lehtimäki, T., Lek, M., Lipscomb, E., Loos, R. J. F., Lu, W., Lubitz, S. A., Luna, T. T., Ma, R. C. W., Marcus, G. M., Marrugat, J., Mattila, K. M., McCarroll, S., McCarthy, M. I., McCauley, J. L., McGovern, D., McPherson, R., Meigs, J. B., Melander, O., Metspalu, A., Meyers, D., Minikel, E. V., Mitchell, B. D., Mootha, V. K., Naheed, A., Nazarian, S., Nilsson, P. M., O’Donovan, M. C., Okada, Y., Ongur, D., Orozco, L., Owen, M. J., Palmer, C., Palmer, N. D., Palotie, A., Park, K. S., Pato, C., Pulver, A. E., Rader, D., Rahman, N., Reiner, A., Remes, A. M., Rhodes, D., Rich, S., Rioux, J. D., Ripatti, S., Roden, D. M., Rotter, J. I., Sahakian, N., Saleheen, D., Salomaa, V., Saltzman, A., Samani, N. J., Samocha, K. E., Sanchis-Juan, A., Scharf, J., Schleicher, M., Schunkert, H., Schönherr, S., Seaby, E. G., Shah, S. H., Shand, M., Sharpe, T., Shoemaker, M. B., Shyong, T., Silverman, E. K., Singer-Berk, M., Sklar, P., Smith, J. T., Smith, J. G., Soininen, H., Sokol, H., Son, R. G., Soto, J., Spector, T., Stevens, C., Stitziel, N. O., Sullivan, P. F., Suvisaari, J., Tai, E. S., Taylor, K. D., Teo, Y. Y., Tsuang, M., Tuomi, T., Turner, D., Tusie-Luna, T., Vartiainen, E., Vawter, M., Wang, L., Wang, A., Ware, J. S., Watkins, H., Weersma, R. K., Weisburd, B., Wessman, M., Whiffin, N., Wilson, J. G., Xavier, R. J., O’Donnell-Luria, A., Solomonson, M., Seed, C., Martin, A. R., Talkowski, M. E., Rehm, H. L., Daly, M. J., Tiao, G., Neale, B. M., MacArthur, D. G., & Karczewski, K. J.
- Affiliations
- Broad Institute (US)
- Lady Davis Institute for Medical Research (CA)
- University of Miami (US)
- Peninsula College of Medicine and Dentistry (GB)
- Brigham and Women's Hospital (US)
- University of Parma (IT)
- Albert Einstein College of Medicine (US)
- Cleveland Clinic (US)
- Sorbonne Université (FR)
- Boston University (US)
- University of Michigan (US)
- National Institutes of Health (US)
- Wake Forest University Health Sciences (US)
- University of Leicester (GB)
- Harvard University (US)
- Rutgers, The State University of New Jersey (US)
- Imperial College Healthcare NHS Trust (GB)
- Chinese University of Hong Kong (HK)
- Northwestern University (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Cambridge (GB)
- Columbia University Irving Medical Center (US)
- University of Mississippi Medical Center (US)
- Colorado School of Public Health (US)
- University of Illinois Chicago (US)
- Vanderbilt University Medical Center (US)
- Texas A&M University – San Antonio (US)
- University of Lübeck (DE)
- Victor Chang Cardiac Research Institute (AU)
- University of Helsinki (FI)
- Boston Children's Hospital (US)
- SUNY Upstate Medical University (US)
- University of Southern California (US)
- Washington University in St. Louis (US)
- The University of Texas Health Science Center at Houston (US)
- Columbia University (US)
- University of Eastern Finland (FI)
- Helsinki University Hospital (FI)
- Karolinska Institutet (SE)
- Korea National Institute of Health (KR)
- Cardiff University (GB)
- Finnish Institute for Health and Welfare (FI)
- Yale New Haven Hospital (US)
- Emory University (US)
- Seoul National University (KR)
- Yale University (US)
- Tampere University (FI)
- University of Copenhagen (DK)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- University of California, San Francisco (US)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Centre for Human Genetics (GB)
- Cedars-Sinai Medical Center (US)
- Ottawa Heart Institute (CA)
- Lund University (SE)
- University of Tartu (EE)
- University of Arizona (US)
- University of Maryland, Baltimore (US)
- International Centre for Diarrhoeal Disease Research (BD)
- Johns Hopkins University (US)
- Institute for Open and Transdisciplinary Research Initiatives (JP)
- National Institute of Genomic Medicine (MX)
- University of Dundee (GB)
- Children's Hospital of Philadelphia (US)
- Institute of Cancer Research (GB)
- University of Washington (US)
- Oulu University Hospital (FI)
- University of Virginia (US)
- Montreal Heart Institute (CA)
- The Lundquist Institute (US)
- Center for Non-Communicable Diseases (PK)
- Deutsches Herzzentrum München (DE)
- Innsbruck Medical University (AT)
- Duke University (US)
- Vanderbilt University (US)
- National University of Singapore (SG)
- Inserm (FR)
- King's College London (GB)
- University of North Carolina at Chapel Hill (US)
- University of California San Diego (US)
- Hebrew University of Jerusalem (IL)
- University of California, Irvine (US)
- University of Oxford (GB)
- University Medical Center Groningen (NL)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Chen, Siwei
- Karczewski, Konrad J.
- ORCID
- Chen, Siwei
- Francioli, Laurent C.
- Goodrich, Julia K.
- Collins, Ryan L.
- Kanai, Masahiro
- Wang, Qingbo
- Alföldi, Jessica
- Poterba, Timothy
- Wilson, Michael W.
- Phu, William
- Farjoun, Yossi
- Banks, Eric
- Donnelly, Stacey
- Gabriel, Stacey
- Gupta, Namrata
- Abreu, Maria
- Ahmad, Tariq
- Albert, Christine M.
- Ardissino, Diego
- Armean, Irina M.
- Atkinson, Elizabeth G.
- Atzmon, Gil
- Barnard, John
- Baxter, Samantha M.
- Beaugerie, Laurent
- Benjamin, Emelia J.
- Boehnke, Michael
- Bonnycastle, Lori L.
- Bowden, Donald W.
- Bown, Matthew J.
- Brand, Harrison
- Brant, Steven
- Calvo, Sarah E.
- Campos, Hannia
- Chambers, John C.
- Chan, Juliana C.
- Chao, Katherine R.
- Chapman, Sinéad
- Chasman, Daniel I.
- Chisholm, Rex
- Cho, Judy
- Chowdhury, Rajiv
- Chung, Mina K.
- Chung, Wendy K.
- Cibulskis, Kristian
- Cohen, Bruce
- Correa, Adolfo
- Cummings, Beryl B.
- Dabelea, Dana
- Danesh, John
- Darbar, Dawood
- Denny, Joshua
- Duggirala, Ravindranath
- Dupuis, Josée
- Ellinor, Patrick T.
- Erdmann, Jeanette
- Esko, Tõnu
- Evangelista, Emily
- Fatkin, Diane
- Fu, Jack
- Färkkilä, Martti
- Garimella, Kiran
- Getz, Gad
- Glahn, David C.
- Glatt, Stephen J.
- Goldstein, David
- Groop, Leif
- Gudmundsson, Sanna
- Haessly, Andrea
- Haiman, Christopher
- Hall, Ira
- Hanis, Craig L.
- Harms, Matthew
- Hiltunen, Mikko
- Holi, Matti M.
- Hultman, Christina M.
- Jalas, Chaim
- Kallela, Mikko
- Kaprio, Jaakko
- Kathiresan, Sekar
- Kenny, Eimear E.
- Kim, Bong-Jo
- Kim, Young Jin
- Kirov, George
- Kooner, Jaspal
- Koskinen, Seppo
- Krumholz, Harlan M.
- Kugathasan, Subra
- Kwak, Soo Heon
- Laakso, Markku
- Lake, Nicole
- Laricchia, Kristen M.
- Lehtimäki, Terho
- Lek, Monkol
- Loos, Ruth J. F.
- Lu, Wenhan
- Lubitz, Steven A.
- Marcus, Gregory M.
- Marrugat, Jaume
- McCarroll, Steven
- McCarthy, Mark I.
- McCauley, Jacob L.
- McGovern, Dermot
- McPherson, Ruth
- Meigs, James B.
- Melander, Olle
- Metspalu, Andres
- Meyers, Deborah
- Minikel, Eric V.
- Mitchell, Braxton D.
- Mootha, Vamsi K.
- Naheed, Aliya
- Nazarian, Saman
- Nilsson, Peter M.
- O’Donovan, Michael C.
- Okada, Yukinori
- Orozco, Lorena
- Owen, Michael J.
- Palotie, Aarno
- Park, Kyong Soo
- Pato, Carlos
- Pulver, Ann E.
- Rahman, Nazneen
- Reiner, Alex
- Rich, Stephen
- Rioux, John D.
- Ripatti, Samuli
- Roden, Dan M.
- Rotter, Jerome I.
- Saleheen, Danish
- Salomaa, Veikko
- Saltzman, Andrea
- Samani, Nilesh J.
- Samocha, Kaitlin E.
- Scharf, Jeremiah
- Schunkert, Heribert
- Schönherr, Sebastian
- Seaby, Eleanor G.
- Shah, Svati H.
- Shand, Megan
- Shoemaker, Moore B.
- Silverman, Edwin K.
- Sklar, Pamela
- Smith, Jonathan T.
- Soininen, Hilkka
- Sokol, Harry
- Son, Rachel G.
- Spector, Tim
- Stevens, Christine
- Stitziel, Nathan O.
- Sullivan, Patrick F.
- Suvisaari, Jaana
- Tai, E. Shyong
- Taylor, Kent D.
- Tsuang, Ming
- Turner, Dan
- Vartiainen, Erkki
- Vawter, Marquis
- Wang, Lily
- Ware, James S.
- Watkins, Hugh
- Weersma, Rinse K.
- Weisburd, Ben
- Whiffin, Nicola
- Wilson, James G.
- Xavier, Ramnik J.
- O’Donnell-Luria, Anne
- Solomonson, Matthew
- Martin, Alicia R.
- Talkowski, Michael E.
- Rehm, Heidi L.
- Daly, Mark J.
- Tiao, Grace
- Neale, Benjamin M.
- MacArthur, Daniel G.
- Karczewski, Konrad J.
- Venue
- Nature
- Published
- 2023-12-06
- Volume
- 625
- Issue
- 7993
- Pages
- 92-100
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC11629659
- OpenAlex
- W4389367121
- Cited by
- 1,727
- References
- 90
- Citations by year
- 2026: 520 · 2025: 642 · 2024: 442 · 2023: 121
- FWCI
- 286.54
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-01-15)
- Open access
- green
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Wellcome Trust (107469/Z/15/Z)
- National Institutes of Health
- Medical Research Council (MR/L010305/1)
- National Institute of Mental Health (R01MH115957)
- National Human Genome Research Institute (U24HG011450)
- National Institute of Diabetes and Digestive and Kidney Diseases (U54DK105566)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD081256)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- purifying selection, non-coding DNA, regulatory elements, gnocchi, allele frequency, complex diseases, genetic variants, protein-coding genes, sequence context
- MeSH terms
- Chromosome Mapping, Gene Frequency, Humans, Models, Genetic, Mutation, Selection, Genetic, Genetic Variation, Genome, Human, Access to Information, Genomics, Databases, Genetic, Datasets as Topic
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
