The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Rate of de novo mutations and the importance of father’s age to disease risk
Open accessAbstract
Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20 × 10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism.
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 cited source says what the claim attributes to it.
In the citing paper
“Recent evidence suggests that de novo mutations that arise in the germline are a significant cause of ASD, although it is important to keep in mind that the genetic aetiology of about 70% of the forms of ASD is unknown and it remains perplexing why ASD is at least four times more prevalent in males than in females.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“These studies demonstrate the ability of new sequencing technologies to significantly advance our understanding of the genetic basis of ASD.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [10]
In the citing paper
“suggesting that the observed SNP heritability for autistic carriers reflects autism rather than factors associated with the generation of germline mutations57,58.”
From Genetic correlates of phenotypic heterogeneity in autism (2022) · cites this paper as [58]
In the citing paper
“We and others have demonstrated that advanced paternal age correlates with increased rates of germline mutation in offspring28–30”
From A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex (2022) · cites this paper as [29]
In the citing paper
“ASD is often due to newly arising gene copy number variants (CNVs) — such as a deletion or duplication of a region of a chromosome — or a rare mutation that arises in the germ cell, particularly in sperm of older fathers5–10.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [10]
In the citing paper
“References 7– 10 use exome and entire genome sequencing to demonstrate the importance of rare mutations in ASD and identify new genetic mutations associated with ASD.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [10]
In the citing paper
“Thus, a majority (70%) of de novo mutations originate from the father and total rate of new mutations in offspring increase by 1–2 mutations per year with his age (Kong et al., 2012; Michaelson et al., 2012).”
From Getting to the cores of autism (2019) · cites this paper as Kong et al., 2012
In the citing paper
“In the Icelandic trios, TCC → TTC and GGA → GAA are ranked 20th and 18th.”
From Evidence for recent, population-specific evolution of the human mutation rate (2015) · cites this paper as [10]
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
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
The 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
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · cited 4×
“Applying (5) eliminated 1,285 candidate mutations (Supplementary Information).”
InfluentialDe novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734
Estimate of the Mutation Rate per Nucleotide in Humans
Nachman, M. W., & Crowell, S. L. (2000) · Genetics · doi:10.1093/genetics/156.1.297 · Cited by 1,226
Molecular basis of base substitution hotspots in Escherichia coli
Coulondre, C., Miller, J. H., Farabaugh, P. J., & Gilbert, W. (1978) · Nature · doi:10.1038/274775a0 · Cited by 1,193
Analysis of Genetic Inheritance in a Family Quartet by Whole-Genome Sequencing
Roach, J. C., Glusman, G., Smit, A. F. A., Huff, C. D., Hubley, R., Shannon, P. T., Rowen, L., Pant, K. P., Goodman, N., Bamshad, M., et al. (2010) · Science · doi:10.1126/science.1186802 · Cited by 1,084
The origins, patterns and implications of human spontaneous mutation
Crow, J. F. (2000) · Nature Reviews Genetics · doi:10.1038/35049558 · Cited by 928
Rate, molecular spectrum, and consequences of human mutation
Lynch, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912629107 · Cited by 792
Cited by
Sorted by citations
The contribution of de novo coding mutations to autism spectrum disorder
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Witherspoon, K. T., Vives, L., Patterson, K. E., et al. (2014) · Nature · doi:10.1038/nature13908 · Cited by 2,585
Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61539-1 · Cited by 2,371
The complete genome sequence of a Neanderthal from the Altai Mountains
Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P. H., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature12886 · Cited by 2,254
Owen, M. J., Sawa, A., & Mortensen, P. B. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01121-6 · Cited by 1,870
Lord, C., Brugha, T. S., Charman, T., Cusack, J., Dumas, G., Frazier, T., Jones, E. J. H., Jones, R. M., Pickles, A., State, M. W., et al. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0138-4 · Cited by 1,859
De novo mutations in schizophrenia implicate synaptic networks
Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., et al. (2014) · Nature · doi:10.1038/nature12929 · Cited by 1,617
Identification, Evaluation, and Management of Children With Autism Spectrum Disorder
Hyman, S. L., Levy, S. E., Myers, S. M., COUNCIL ON CHILDREN WITH DISABILITIES, S. O. D. A. B. P., Kuo, D. Z., Apkon, S., Davidson, L. F., Ellerbeck, K. A., Foster, J. E. A., Noritz, G. H., et al. (2020) · Pediatrics · doi:10.1542/peds.2019-3447 · Cited by 1,798
De novo mutations in epileptic encephalopathies
Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514
Prevalence and architecture of de novo mutations in developmental disorders
Study, D. D. D. (2017) · Nature · doi:10.1038/nature21062 · Cited by 1,480
Robust Demographic Inference from Genomic and SNP Data
Excoffier, L., Dupanloup, I., Huerta‐Sánchez, E., Sousa, V. C., & Foll, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003905 · Cited by 1,480
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders
O’Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. (2012) · Science · doi:10.1126/science.1227764 · Cited by 1,240
Genome sequencing identifies major causes of severe intellectual disability
Gilissen, C., Hehir-Kwa, J. Y., Thung, D. T., van de Vorst, M., van Bon, B. W. M., Willemsen, M. H., Kwint, M., Janssen, I. M., Hoischen, A., Schenck, A., et al. (2014) · Nature · doi:10.1038/nature13394 · Cited by 1,125
The Next-Generation Sequencing Revolution and Its Impact on Genomics
Koboldt, D. C., Steinberg, K. M., Larson, D. E., Wilson, R. K., & Mardis, E. R. (2013) · Cell · doi:10.1016/j.cell.2013.09.006 · Cited by 1,098
Byrska-Bishop, M., Evani, U. S., Zhao, X., Basile, A. O., Abel, H. J., Regier, A. A., Corvelo, A., Clarke, W. E., Musunuri, R., Nagulapalli, K., et al. (2022) · Cell · doi:10.1016/j.cell.2022.08.004 · Cited by 1,094
Inferring human population size and separation history from multiple genome sequences
Schiffels, S., & Durbin, R. (2014) · Nature Genetics · doi:10.1038/ng.3015 · Cited by 1,073
Clock-like mutational processes in human somatic cells
Alexandrov, L. B., Jones, P. H., Wedge, D. C., Sale, J. E., Campbell, P. J., Nik‐Zainal, S., & Stratton, M. R. (2015) · Nature Genetics · doi:10.1038/ng.3441 · Cited by 1,065
Rimmer, A., Phan, H. T. T., Mathieson, I., Iqbal, Z., Twigg, S. R. F., Wilkie, A. O. M., McVean, G., & Lunter, G. A. (2014) · Nature Genetics · doi:10.1038/ng.3036 · Cited by 1,049
Genome sequence of a 45,000-year-old modern human from western Siberia
Fu, Q., Li, H., Moorjani, P., Jay, F., Slepchenko, S. M., Bondarev, A. A., Johnson, P. L. F., Aximu-Petri, A., Prüfer, K., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature13810 · Cited by 1,023
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
From the genetic architecture to synaptic plasticity in autism spectrum disorder
Bourgeron, T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3992 · Cited by 975
Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., Reilly, S. K., Lin, L., Fertuzinhos, S., Miller, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.020 · Cited by 934
De novo mutations in histone-modifying genes in congenital heart disease
Zaidi, S., Choi, M., Wakimoto, H., Ma, L., Jiang, J., Overton, J. D., Romano-Adesman, A., Bjornson, R. D., Breitbart, R. E., Brown, K. K., et al. (2013) · Nature · doi:10.1038/nature12141 · Cited by 934
Inferring the molecular and phenotypic impact of amino acid variants with MutPred2
Pejaver, V., Urresti, J., Lugo-Martinez, J., Pagel, K. A., Lin, G. N., Nam, H.-J., Mort, M., Cooper, D. N., Sebat, J., Iakoucheva, L. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19669-x · Cited by 923
Oxidative stress and male infertility
Bisht, S., Faiq, M. A., Tolahunase, M., & Dada, R. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.69 · Cited by 918
Genetic drift, selection and the evolution of the mutation rate
Lynch, M., Ackerman, M. S., Gout, J.-F., Long, H., Sung, W., Thomas, W. K., & Foster, P. L. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.104 · Cited by 911
DNA methylation: a historical perspective
Mattei, A. L., Bailly, N., & Meissner, A. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.03.010 · Cited by 920
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
C Yuen, R. K., Merico, D., Bookman, M., L Howe, J., Thiruvahindrapuram, B., Patel, R. V., Whitney, J., Deflaux, N., Bingham, J., Wang, Z., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4524 · Cited by 844
Genetic studies in intellectual disability and related disorders
Vissers, L. E. L. M., Gilissen, C., & Veltman, J. A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg3999 · Cited by 761
A Revised Timescale for Human Evolution Based on Ancient Mitochondrial Genomes
Fu, Q., Mittnik, A., Johnson, P. L. F., Bos, K., Lari, M., Bollongino, R., Sun, C., Giemsch, L., Schmitz, R., Burger, J., et al. (2013) · Current Biology · doi:10.1016/j.cub.2013.02.044 · Cited by 709
Genetics of autism spectrum disorders
Geschwind, D. H. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.07.003 · Cited by 696
Activity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666
Francioli, L. C., Menelaou, A., Pulit, S. L., Elbers, C. C., Kloosterman, W. P., van Setten, J., Nijman, I. J., Renkens, I., de Bakker, P. I. W., van Dijk, F., et al. (2014) · Nature Genetics · doi:10.1038/ng.3021 · Cited by 651
Timing, rates and spectra of human germline mutation
Rahbari, R., Wüster, A., Lindsay, S., Hardwick, R. J., Alexandrov, L. B., Turki, S. H. A., Dominiczak, A. F., Morris, A. D., Porteous, D. J., Smith, B. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3469 · Cited by 641
Oxidative stress and male reproductive health
Aitken, R. J., Smith, T., Jobling, M. S., Baker, M., & Iuliis, G. N. D. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122203 · Cited by 637
Genetic Causes and Modifiers of Autism Spectrum Disorder
Rylaarsdam, L. E., & Guemez‐Gamboa, A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00385 · Cited by 618
Genetics and Genomics of Congenital Heart Disease
Zaidi, S., & Brueckner, M. K. (2017) · Circulation Research · doi:10.1161/circresaha.116.309140 · Cited by 612
Parental influence on human germline de novo mutations in 1,548 trios from Iceland
Jónsson, H., Sulem, P., Kehr, B., Kristmundsdottir, S., Zink, F., Hjartarson, E., Hardarson, M. T., Hjorleifsson, K. E., Eggertsson, H. P., Gudjonsson, S. A., et al. (2017) · Nature · doi:10.1038/nature24018 · Cited by 561
Self-citationThe dysconnection hypothesis (2016)
Friston, K., Brown, H. R., Siemerkus, J., & Stephan, K. E. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.07.014 · Cited by 561
Somatic mutation landscapes at single-molecule resolution
Abascal, F., Harvey, L. M. R., Mitchell, E., Lawson, A. R. J., Lensing, S. V., Ellis, P., Russell, A. J. C., Alcantara, R. E., Baez-Ortega, A., Wang, Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03477-4 · Cited by 546
Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation
Michaelson, J. J., Shi, Y., Gujral, M., Zheng, H., Malhotra, D., Jin, X., Jian, M., Liu, G., Greer, D., Bhandari, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.019 · Cited by 544
Eisenberg, M. L., Esteves, S. C., Lamb, D. J., Hotaling, J. M., Giwercman, A., Hwang, K., & Cheng, Y.-S. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00459-w · Cited by 536
Gulsuner, S., Walsh, T., Watts, A. C., Lee, M. K., Thornton, A. M., Casadei, S., Rippey, C., Shahin, H., Braff, D., Cadenhead, K. S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.049 · Cited by 536
Examining and interpreting the female protective effect against autistic behavior
Robinson, E. B., Lichtenstein, P., Anckarsäter, H., Happé, F., & Ronald, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211070110 · Cited by 531
The contribution of environmental exposure to the etiology of autism spectrum disorder
Bölte, S., Girdler, S., & Marschik, P. B. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2988-4 · Cited by 509
Sharma, R. K., Agarwal, A. K., Rohra, V. K., Assidi, M., Abu-Elmagd, M. M., & Turki, R. F. (2015) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-015-0028-x · Cited by 486
The Genetic Landscapes of Autism Spectrum Disorders
Huguet, G., Ey, E., & Bourgeron, T. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153431 · Cited by 486
Exploring population size changes using SNP frequency spectra
Liu, X., & Fu, Y. (2015) · Nature Genetics · doi:10.1038/ng.3254 · Cited by 481
Jiang, Y.-H., Yuen, R. K. C., Jin, X., Wang, M., Chen, N., Wu, X., Ju, J., Mei, J., Shi, Y., He, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.06.012 · Cited by 474
New insights into the generation and role of de novo mutations in health and disease
Acuña‐Hidalgo, R., Veltman, J. A., & Hoischen, A. (2016) · Genome biology · doi:10.1186/s13059-016-1110-1 · Cited by 474
Genomic signatures of selection at linked sites: unifying the disparity among species
Cutter, A. D., & Payseur, B. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3425 · Cited by 467
Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals
Vernot, B., Tucci, S., Kelso, J., Schraiber, J. G., Wolf, A. B., Gittelman, R. M., Dannemann, M., Grote, S., McCoy, R. C., Norton, H., et al. (2016) · Science · doi:10.1126/science.aad9416 · Cited by 459
Inherited and de novo genetic risk for autism impacts shared networks
Ruzzo, E. K., Pérez-Cano, L., Jung, J.-Y., Wang, L.-K., Kashef-Haghighi, D., Hartl, C., Singh, C., Xu, J., Hoekstra, J. N., Leventhal, O., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.015 · Cited by 457
Broer, L., Codd, V., Nyholt, D. R., Deelen, J., Mangino, M., Willemsen, G., Albrecht, E., Amin, N., Beekman, M., de Geus, E. J. C., et al. (2013) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.303 · Cited by 450
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
Hamdan, F. F., Myers, C. T., Cossette, P., Lemay, P., Spiegelman, D., Laporte, A. D., Nassif, C., Diallo, O., Monlong, J., Cadieux-Dion, M., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.09.008 · Cited by 445
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
Lelieveld, S. H., Reijnders, M. R. F., Pfundt, R., Yntema, H. G., Kamsteeg, E.-J., de Vries, P., de Vries, B. B. A., Willemsen, M. H., Kleefstra, T., Löhner, K., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4352 · Cited by 442
Brownstein, C. A., Beggs, A. H., Homer, N., Merriman, B., Yu, T. W., Flannery, K. C., DeChene, E. T., Towne, M. C., Savage, S. K., Price, E., et al. (2014) · Genome biology · doi:10.1186/gb-2014-15-3-r53 · Cited by 435
Differences between germline and somatic mutation rates in humans and mice
Milholland, B., Dong, X., Zhang, L., Hao, X., Suh, Y., & Vijg, J. (2017) · Nature Communications · doi:10.1038/ncomms15183 · Cited by 429
Precise estimates of mutation rate and spectrum in yeast
Zhu, Y. O., Siegal, M. L., Hall, D. W., & Petrov, D. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323011111 · Cited by 429
Fathers’ Roles in the Care and Development of Their Children: The Role of Pediatricians
Yogman, M. W., Garfield, C. F., Bauer, N. S., Gambon, T. B., Lavin, A., Lemmon, K. M., Mattson, G. L., Rafferty, J. R., EdM, & Wissow, L. S. (2016) · PEDIATRICS · doi:10.1542/peds.2016-1128 · Cited by 422
Consistent age-dependent declines in human semen quality: A systematic review and meta-analysis
Johnson, S. L., Dunleavy, J. E. M., Gemmell, N. J., & Nakagawa, S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.10.007 · Cited by 397
The role of de novo mutations in the genetics of autism spectrum disorders
Ronemus, M., Iossifov, I., Levy, D., & Wigler, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3585 · Cited by 390
Environmental factors in declining human fertility
Skakkebæk, N. E., Lindahl-Jacobsen, R., Levine, H., Andersson, A.-M., Jørgensen, N., Main, K. M., Lidegaard, Ø., Priskorn, L., Holmboe, S. A., Bräuner, E. V., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00598-8 · Cited by 389
The presence, role and clinical use of spermatozoal RNAs
Jodar, M., Selvaraju, S., Sendler, E. D., Diamond, M. P., Krawetz, S. A., & for the Reproductive Medicine Network (2013) · Human Reproduction Update · doi:10.1093/humupd/dmt031 · Cited by 387
Genome-wide patterns and properties of de novo mutations in humans
Francioli, L. C., Polak, P. P., Koren, A., Menelaou, A., Chun, S., Renkens, I., van Duijn, C. M., Swertz, M. A., Wijmenga, C., van Ommen, G. B., et al. (2015) · Nature Genetics · doi:10.1038/ng.3292 · Cited by 383
Early human dispersals within the Americas
Moreno-Mayar, J. V., Vinner, L., Damgaard, P. D. B., Castro, C. D. L. F., Chan, J., Spence, J. P., Allentoft, M. E., Vimala, T., Racimo, F., Pinotti, T., et al. (2018) · Science · doi:10.1126/science.aav2621 · Cited by 383
The mutational landscape of human somatic and germline cells
Moore, L., Cagan, A., Coorens, T. H. H., Neville, M. D. C., Sanghvi, R., Sanders, M. A., Oliver, T. R. W., Leongamornlert, D., Ellis, P., Noorani, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03822-7 · Cited by 379
Genome-Wide Inference of Ancestral Recombination Graphs
Rasmussen, M. D., Hubisz, M. J., Gronau, I., & Siepel, A. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004342 · Cited by 371
Evolution of the germline mutation rate across vertebrates
Bergeron, L. A., Besenbacher, S., Zheng, J., Li, P., Bertelsen, M. F., Quintard, B., Hoffman, J. I., Li, Z., Leger, J. S., Shao, C., et al. (2023) · Nature · doi:10.1038/s41586-023-05752-y · Cited by 387
Self-citationLarge-scale genomics unveils the genetic architecture of psychiatric disorders
Gratten, J., Wray, N. R., Keller, M. C., & Visscher, P. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3708 · Cited by 363
Characterizing mutagenic effects of recombination through a sequence-level genetic map
Halldórsson, B. V., Pálsson, G., Stefánsson, Ó. A., Jónsson, H., Hardarson, M. T., Eggertsson, H. P., Gunnarsson, B., Oddsson, Á., Halldorsson, G. H., Zink, F., et al. (2019) · Science · doi:10.1126/science.aau1043 · Cited by 366
Self-citationIndividualized Medicine from Prewomb to Tomb
Topol, E. J. (2014) · Cell · doi:10.1016/j.cell.2014.02.012 · Cited by 358
A direct characterization of human mutation based on microsatellites
Sun, J. X., Helgason, A., Másson, G., Ebenesersdóttir, S. S., Li, H., Mallick, S., Gnerre, S., Patterson, N. J., Kong, A., Reich, D., et al. (2012) · Nature Genetics · doi:10.1038/ng.2398 · Cited by 348
Self-citationGlobal diversity, population stratification, and selection of human copy-number variation
Sudmant, P. H., Mallick, S., Nelson, B. J., Hormozdiari, F., Krumm, N., Huddleston, J., Coe, B. P., Baker, C., Nordenfelt, S., Bamshad, M., et al. (2015) · Science · doi:10.1126/science.aab3761 · Cited by 345
DNA Methylation, Its Mediators and Genome Integrity
Meng, H., Cao, Y., Qin, J., Song, X., Zhang, Q., Shi, Y. S., & Cao, L. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.11218 · Cited by 346
Genomic Patterns of De Novo Mutation in Simplex Autism
Turner, T. N., Coe, B. P., Dickel, D. E., Hoekzema, K., Nelson, B. J., Zody, M. C., Kronenberg, Z. N., Hormozdiari, F., Raja, A. N., Pennacchio, L. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.047 · Cited by 343
Kosmicki, J. A., Samocha, K. E., Howrigan, D. P., Sanders, S. J., Slowikowski, K., Lek, M., Karczewski, K. J., Cutler, D. J., Devlin, B., Roeder, K., et al. (2017) · Nature Genetics · doi:10.1038/ng.3789 · Cited by 340
Parent-of-origin-specific signatures of de novo mutations
Goldmann, J. M., Wong, W. S. W., Pinelli, M., Farrah, T., Bodian, D. L., Stittrich, A., Glusman, G., Vissers, L. E. L. M., Hoischen, A., Roach, J. C., et al. (2016) · Nature Genetics · doi:10.1038/ng.3597 · Cited by 340
Self-citationMcCarthy, S. E., Gillis, J., Kramer, M., Lihm, J., Yoon, S. C., Berstein, Y., Mistry, M., Pavlidis, P., Solomon, R., Ghiban, E., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.29 · Cited by 338
An Evolutionary Life History Framework for Psychopathology
Giudice, M. D. (2014) · Psychological Inquiry · doi:10.1080/1047840x.2014.884918 · Cited by 335
Genome-wide profiling of heritable and de novo STR variations
Willems, T., Zielinski, D., Yuan, J., Gordon, A., Gymrek, M., & Erlich, Y. (2017) · Nature Methods · doi:10.1038/nmeth.4267 · Cited by 329
Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder
An, J.-Y., Lin, K., Zhu, L., Werling, D. M., Dong, S., Brand, H., Wang, H. Z., Zhao, X., Schwartz, G. B., Collins, R. L., et al. (2018) · Science · doi:10.1126/science.aat6576 · Cited by 316
Relatedness in the post-genomic era: is it still useful?
Speed, D., & Balding, D. J. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3821 · Cited by 316
Effects of aging on the male reproductive system
Gunes, S. O., Hekim, N., Arslan, M. A., & Aşçı, R. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0663-y · Cited by 320
Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations
Esteves, S. C., Zini, A. S., Coward, R. M., Evenson, D. P., Gosálvez, J., Lewis, S. E. M., Sharma, R. K., & Humaidan, P. (2020) · Andrologia · doi:10.1111/and.13874 · Cited by 313
Autism risk associated with parental age and with increasing difference in age between the parents
Sandin, S., Schendel, D., Magnusson, P. K. E., Hultman, C. M., Surén, P., Susser, E., Grønborg, T. K., Gissler, M., Gunnes, N., Gross, R., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.70 · Cited by 313
He, X., Sanders, S. J., Liu, L., De Rubeis, S., Lim, E. T., Sutcliffe, J. S., Schellenberg, G. D., Gibbs, R. A., Daly, M. J., Buxbaum, J. D., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003671 · Cited by 304
Parenting from before conception
Lane, M., Robker, R. L., & Robertson, S. A. (2014) · Science · doi:10.1126/science.1254400 · Cited by 304
Keightley, P. D., Ness, R. W., Halligan, D. L., & Haddrill, P. R. (2013) · Genetics · doi:10.1534/genetics.113.158758 · Cited by 304
A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy
Muona, M., Berkovic, S. F., Dibbens, L. M., Oliver, K. L., Maljevic, S., Bayly, M. A., Joensuu, T. H., Canafoglia, L., Franceschetti, S., Michelucci, R., et al. (2014) · Nature Genetics · doi:10.1038/ng.3144 · Cited by 299
Somatic mosaicism: implications for disease and transmission genetics
Campbell, I. M., Shaw, C. A., Stankiewicz, P., & Lupski, J. R. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.013 · Cited by 296
Lewis, S. E. M., Aitken, R. J., Conner, S. J., Iuliis, G. N. D., Evenson, D. P., Henkel, R., Giwercman, A., & Gharagozloo, P. (2013) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2013.06.014 · Cited by 292
Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk
Zhou, J., Park, C. Y., Theesfeld, C. L., Wong, A. K., Yuan, Y., Scheckel, C., Fak, J. J., Funk, J., Yao, K., Tajima, Y., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0420-0 · Cited by 295
Exome sequencing reveals new causal mutations in children with epileptic encephalopathies
Veeramah, K. R., Johnstone, L. M., Karafet, T. M., Wolf, D., Sprissler, R. S., Salogiannis, J., Barth‐Maron, A., Greenberg, M. E., Stuhlmann, T., Weinert, S., et al. (2013) · Epilepsia · doi:10.1111/epi.12201 · Cited by 294
Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective
Brown, A. S., & Meyer, U. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17121311 · Cited by 294
Werling, D. M., Brand, H., An, J.-Y., Stone, M. R., Zhu, L., Glessner, J. T., Collins, R. L., Dong, S., Layer, R. M., Markenscoff-Papadimitriou, E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0107-y · Cited by 293
Properties and rates of germline mutations in humans
Campbell, C. D., & Eichler, E. E. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.04.005 · Cited by 292
Determinants of Mutation Rate Variation in the Human Germline
Ségurel, L., Wyman, M. J., & Przeworski, M. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-031714-125740 · Cited by 289
Environmental factors influencing the risk of autism
Karimi, P., Kamali, E., Mousavi, S. M., & Karahmadi, M. (2017) · Journal of Research in Medical Sciences · doi:10.4103/1735-1995.200272 · Cited by 289
Early Neolithic genomes from the eastern Fertile Crescent
Broushaki, F., Thomas, M. G., Link, V., López, S., van Dorp, L., Kirsanow, K., Hofmanová, Z., Diekmann, Y., Cassidy, L. M., Díez-del-Molino, D., et al. (2016) · Science · doi:10.1126/science.aaf7943 · Cited by 288
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies
Myers, C. T., McMahon, J. M., Schneider, A. L., Petrovski, S., Allen, A. S., Carvill, G. L., Zemel, M., Saykally, J. E., LaCroix, A. J., Heinzen, E. L., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.06.003 · Cited by 287
Metadata
- Authors
- Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., Wong, W. S. W., Sigurdsson, G., Walters, G. B., Steinberg, S., Helgason, H., Thorleifsson, G., Gudbjartsson, D. F., Helgason, A., Magnusson, O. T., Thorsteinsdottir, U., & Stefansson, K.
- Affiliations
- deCODE Genetics (Iceland) (IS)
- Illumina (United Kingdom) (GB)
- Corresponding author
- Kong, Augustine
- ORCID
- Venue
- Nature
- Published
- 2012-08
- Volume
- 488
- Issue
- 7412
- Pages
- 471-475
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3548427
- OpenAlex
- W2020331089
- Cited by
- 2,134
- References
- 27
- Citations by year
- 2026: 83 · 2025: 95 · 2024: 113 · 2023: 109 · 2022: 128 · 2021: 147 · 2020: 175 · 2019: 154 · 2018: 149 · 2017: 167 · 2016: 180 · 2015: 186 · 2014: 209 · 2013: 188 · 2012: 46
- FWCI
- 120.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH071425, MH071425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- de novo mutations, mutation rate, paternal age, single nucleotide polymorphisms, parent-offspring trios, schizophrenia, autism spectrum disorder, disease risk, demographic transition, Icelandic population
- MeSH terms
- Adult, Autistic Disorder, Chromosomes, Human, Female, Humans, Iceland, Male, Middle Aged, Mothers, Ovum, Paternal Age, Pedigree, Risk Factors, Schizophrenia, Selection, Genetic, Spermatozoa, Genome, Human, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Young Adult, Mutation Rate
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
