CoChat
Sign Up
Cited by 161Genetic Associations and EpidemiologyGenomics and Rare DiseasesGenetics and Physical Performance

Unique roles of rare variants in the genetics of complex diseases in humans

Open access
Momozawa, Yukihide, Mizukami, Keijiro·2021·Journal of Human Genetics
DOI 10.1038/s10038-020-00845-2PMC PMC7728599
Open this paper in CoChat — free accountOpen PDF

Abstract

Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arrays. Rare variants sequencing analysis mainly revealed have played unique roles in the genetics of complex diseases in humans due to their distinctive features, in contrast to common variants. Unique roles are hypothesis-free evidence for gene causality, a precise target of functional analysis for understanding disease mechanisms, a new favorable target for drug development, and a genetic marker with high disease risk for personalized medicine. As whole-genome sequencing continues to identify more rare variants, the roles associated with rare variants will also increase. However, a better estimation of the functional impact of rare variants across whole genome is needed to enhance their contribution to improvements in human health.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s10038-020-00845-2

Cites

17 of 17 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Rare genetic variants tend to have greater population specificity, making replication of findings from rare variant analyses more difficult.

    “Rare genetic variants tend to have greater population specificity87, making replication of findings from rare variant analyses more difficult.”

    From Genetic determinants of plasma protein levels in the Estonian population (2024) · cites this paper as [87]

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

Flagged first, then by citations

Research works printed but not linked: 113

  1. [1]Tam V Patel N Turcotte M Bossé Y Paré G Meyre D Benefits and limitations of genome-wide association studies Nat Rev Genet 2019 20 467 84 31068683
  2. [2]Visscher PM Wray NR Zhang Q Sklar P McCarthy MI Brown MA 10 years of GWAS discovery: biology, function, and translation Am J Hum Genet 2017 101 5 22 28686856 PMC5501872
  3. [5]Voight BF Kang H Ding J Palmer CD Sidore C Chines PS The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits PLoS Genet 2012 8 e1002793 22876189 PMC3410907
  4. [6]Bahcall O. COGS project and design of the iCOGS array. Nat Genet. 2013. 10.1038/ngicogs.4. · DOI
  5. [7]Das S Abecasis GR Browning BL Genotype imputation from large reference panels Annu Rev Genom Hum Genet 2018 19 73 96 29799802
  6. [8]McCarthy S Das S Kretzschmar W Delaneau O Wood AR Teumer A A reference panel of 64,976 haplotypes for genotype imputation Nat Genet 2016 48 1279 83 27548312 PMC5388176
  7. [9]Claussnitzer M Cho JH Collins R Cox NJ Dermitzakis ET Hurles ME A brief history of human disease genetics Nature. 2020 577 179 89 31915397 PMC7405896
  8. [10]Kowalski MH Qian H Hou Z Rosen JD Tapia AL Shan Y Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations PLoS Genet 2019 15 e1008500 31869403 PMC6953885
  9. [11]Venkataraman GR Rivas MA Rare and common variant discovery in complex disease: the IBD case study Hum Mol Genet 2019 28 R162 R69 31363759 PMC6872431
  10. [12]Hunter DJ Altshuler D Rader DJ From Darwin’s finches to canaries in the coal mine—mining the genome for new biology N Engl J Med 2008 358 2760 63 18579810
  11. [13]Hugot JP Chamaillard M Zouali H Lesage S Cezard JP Belaiche J Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease Nature. 2001 411 599 603 11385576
  12. [14]Ogura Y Bonen DK Inohara N Nicolae DL Chen FF Ramos R A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease Nature. 2001 411 603 6 11385577
  13. [15]Rioux JD Xavier RJ Taylor KD Silverberg MS Goyette P Huett A Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis Nat Genet 2007 39 596 604 17435756 PMC2757939
  14. [16]Libioulle C Louis E Hansoul S Sandor C Farnir F Franchimont D Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4 PLoS Genet 2007 3 e58 17447842 PMC1853118
  15. [17]Consortium TWTCC. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls Nature. 2007 447 661 78 17554300 PMC2719288
  16. [18]Duerr RH Taylor KD Brant SR Rioux JD Silverberg MS Daly MJ A genome-wide association study identifies IL23R as an inflammatory bowel disease gene Science. 2006 314 1461 3 17068223 PMC4410764
  17. [19]Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease Nat Genet 2008 40 955 62 18587394 PMC2574810
  18. [20]Kathiresan S Willer CJ Peloso GM Demissie S Musunuru K Schadt EE Common variants at 30 loci contribute to polygenic dyslipidemia Nat Genet 2008 41 56 65 19060906 PMC2881676
  19. [21]Study C Houlston RS Webb E Broderick P Pittman AM Bernardo M Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer Nat Genet 2008 40 1426 35 19011631 PMC2836775
  20. [22]Spain SL Barrett JC Strategies for fine-mapping complex traits Hum Mol Genet 2015 24 R111 9 26157023 PMC4572002
  21. [24]Momozawa Y Mni M Nakamura K Coppieters W Almer S Amininejad L Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease Nat Genet 2011 43 43 7 21151126
  22. [25]Rivas MA Beaudoin M Gardet A Stevens C Sharma Y Zhang CK Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease Nat Genet 2011 43 1066 73. 21983784 PMC3378381
  23. [27]Bomba L Walter K Soranzo N The impact of rare and low-frequency genetic variants in common disease Genome Biol 2017 18 77 28449691 PMC5408830
  24. [28]Povysil G Petrovski S Hostyk J Aggarwal V Allen AS Goldstein DB Rare-variant collapsing analyses for complex traits: guidelines and applications Nat Rev Genet 2019 20 1 13 31605095
  25. [29]Singh T Walters JTR Johnstone M Curtis D Suvisaari J Torniainen M The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability Nat Genet 2017 49 1167 73 28650482 PMC5533219
  26. [30]Allen AS Bellows ST Berkovic SF Bridgers J Burgess R Cavalleri G Ultra-rare genetic variation in common epilepsies: a case-control sequencing study Lancet Neurol 2017 16 135 43 28102150
  27. [31]Momozawa Y Dmitrieva J Theatre E Deffontaine V Rahmouni S Charloteaux B IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes Nat Commun 2018 9 2427 29930244 PMC6013502
  28. [32]Motegi T Kochi Y Matsuda K Kubo M Yamamoto K Momozawa Y Identification of rare coding variants in TYK2 protective for rheumatoid arthritis in the Japanese population and their effects on cytokine signalling Ann Rheum Dis 2019 78 1062 69 31118190
  29. [33]Toma C Torrico B Hervás A Valdés-Mas R Tristán-Noguero A Padillo V Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations Mol Psychiatry 2013 19 784 90 23999528
  30. [34]Gelfman S Dugger S de Moreno C Ren Z Wolock CJ Shneider NA A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS Genome Res 2019 29 809 18 30940688 PMC6499321
  31. [35]McCarroll SA Huett A Kuballa P Chilewski SD Landry A Goyette P Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease Nat Genet 2008 40 1107 12 19165925 PMC2731799
  32. [36]Brest P Lapaquette P Souidi M Lebrigand K Cesaro A Vouret-Craviari V A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn’s disease Nat Genet 2011 43 242 45 21278745
  33. [37]Fischer J Koch L Emmerling C Vierkotten J Peters T Brüning JC Inactivation of the Fto gene protects from obesity Nature 2009 458 894 98 19234441
  34. [38]Church C Moir L McMurray F Girard C Banks GT Teboul L Overexpression of Fto leads to increased food intake and results in obesity Nat Genet 2010 42 1086 92 21076408 PMC3018646
  35. [39]Smemo S Tena JJ Kim K-H Gamazon ER Sakabe NJ Gómez-Marín C Obesity-associated variants within FTO form long-range functional connections with IRX3 Nature 2014 507 371 75 24646999 PMC4113484
  36. [40]Cao Z Conway KL Heath RJ Rush JS Leshchiner ES Ramirez-Ortiz ZG Ubiquitin Ligase TRIM62 regulates CARD9-mediated anti-fungal immunity and intestinal inflammation Immunity. 2015 43 715 26 26488816 PMC4672733
  37. [41]Corbin LJ Tan VY Hughes DA Wade KH Paul DS Tansey KE Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference Nat Commun 2018 9 711 29459775 PMC5818506
  38. [42]Dendrou CA Cortes A Shipman L Evans HG Attfield KE Jostins L Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity Sci Transl Med 2016 8 363ra149 27807284 PMC5737835
  39. [43]King EA Davis WJ Degner JF Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval PLoS Genet 2019 15 e1008489 31830040 PMC6907751
  40. [45]Plenge RM Scolnick EM Altshuler D Validating therapeutic targets through human genetics Nat Rev Drug Discov 2013 12 581 94 23868113
  41. [46]Cohen JC Boerwinkle E Mosley TH Hobbs HH Sequence variations in PCSK9, low LDL, and protection against coronary heart disease N Engl J Med 2006 354 1264 72 16554528
  42. [48]DeBoever C Tanigawa Y Lindholm ME McInnes G Lavertu A Ingelsson E Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study Nat Commun 2018 9 1612 29691392 PMC5915386
  43. [50]Narasimhan VM Hunt KA Mason D Baker CL Karczewski KJ Barnes MR Health and population effects of rare gene knockouts in adult humans with related parents Science. 2016 352 474 77 26940866 PMC4985238
  44. [51]Feagan BG Sandborn WJ D’Haens G Panés J Kaser A Ferrante M Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study Lancet. 2017 389 1699 709 28411872
  45. [52]Easton DF Pharoah PD Antoniou AC Tischkowitz M Tavtigian SV Nathanson KL Gene-panel sequencing and the prediction of breast-cancer risk N Engl J Med 2015 372 2243 57 26014596 PMC4610139
  46. [53]Cohen SA Pritchard CC Jarvik GP Lynch syndrome: from screening to diagnosis to treatment in the era of modern molecular oncology Annu Rev Genom Hum Genet 2019 20 1 15 30848956
  47. [54]Trinder M Francis GA Brunham LR Association of monogenic vs polygenic hypercholesterolemia with risk of atherosclerotic cardiovascular disease JAMA Cardiol 2020 5 390 99 32049305 PMC7042820
  48. [55]Kuchenbaecker KB Hopper JL Barnes DR Phillips K-A Mooij TM Roos-Blom M-J Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers JAMA. 2017 317 2402 16 28632866
  49. [56]Robson M Im S-A Senkus E Xu B Domchek SM Masuda N Olaparib for metastatic breast cancer in patients with a germline BRCA mutation N Engl J Med 2017 377 523 33 28578601
  50. [57]Daly MB Pilarski R Yurgelun MB Berry MP Buys SS Dickson P NCCN guidelines insights: genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 1.2020 J Natl Compr Canccer Netw 2020 18 380 91 32259785
  51. [58]Momozawa Y Iwasaki Y Parsons MT Kamatani Y Takahashi A Tamura C Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls Nat Commun 2018 9 4083 30287823 PMC6172276
  52. [59]Fujita M, Liu X, Iwasaki Y, Terao C, Takata S, Inai C, et al. Population-wide screening for germline variants of hereditary cancer genes in 12K unselected Japanese colorectal cancers and 27K controls. https://www.biorxiv.org/content/10.1101/2020.03.15.989947v1.full.pdf. 2020. · DOI
  53. [60]Landrum MJ Lee JM Benson M Brown G Chao C Chitipiralla S ClinVar: public archive of interpretations of clinically relevant variants Nucleic Acids Res 2016 44 D862 8 26582918 PMC4702865
  54. [61]Wappenschmidt B Becker AA Hauke J Weber U Engert S Kohler J Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction PLoS ONE 2012 7 e50800 23239986 PMC3519833
  55. [62]Amendola LM Jarvik GP Leo MC McLaughlin HM Akkari Y Amaral MD Performance of ACMG-AMP variant-interpretation guidelines among nine laboratories in the Clinical Sequencing Exploratory Research Consortium Am J Hum Genet 2016 98 1067 76 27181684 PMC4908185
  56. [63]Tayoun AN Pesaran T DiStefano MT Oza A Rehm HL Biesecker LG Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion Hum Mutat 2018 39 1517 24 30192042 PMC6185798
  57. [64]Rebbeck TR Friebel TM Friedman E Hamann U Huo D Kwong A Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations Hum Mutat 2018 39 593 620 29446198 PMC5903938
  58. [65]Roa BB Boyd AA Volcik K Richards SC Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2 Nat Genet 1996 14 185 87 8841191
  59. [66]Maxwell KN Domchek SM Nathanson KL Robson ME Population frequency of germline BRCA1/2 mutations J Clin Oncol 2016 34 4183 85 27551127
  60. [67]Consortium C CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies Am J Hum Genet 2004 74 1175 82 15122511 PMC1182081
  61. [68]Zhang G Zeng Y Liu Z Wei W Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk Tumour Biol 2013 34 2753 57 23765759
  62. [69]Cybulski C Wokołorczyk D Kluźniak W Jakubowska A Górski B Gronwald J An inherited NBN mutation is associated with poor prognosis prostate cancer Br J Cancer 2012 108 461 8 23149842 PMC3566821
  63. [70]Momozawa Y Iwasaki Y Hirata M Liu X Kamatani Y Takahashi A Germline pathogenic variants in 7,636 Japanese patients with prostate cancer and 12,366 controls J Natl Cancer Inst 2020 112 369 76 31214711 PMC7156928
  64. [71]Liu X Takata S Ashikawa K Aoi T Kosugi S Terao C Prevalence and spectrum of pathogenic germline variants in Japanese Patients with early-onset colorectal, breast, and prostate cancer JCO Precis Oncol 2020 4 183 91 35050733
  65. [72]Hayano T Matsui H Nakaoka H Ohtake N Hosomichi K Suzuki K Germline variants of prostate cancer in Japanese families PLOS ONE 2016 11 e0164233 27701467 PMC5049788
  66. [73]Hu C Hart SN Polley EC Gnanaolivu R Shimelis H Lee KY Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer JAMA. 2018 319 2401 09 29922827 PMC6092184
  67. [75]Manchanda R Lieberman S Gaba F Lahad A Levy-Lahad E Population screening for inherited predisposition to breast and ovarian cancer. Annu Rev Genom Hum Genet 2020 21 373 412 32315550
  68. [76]Ceyhan-Birsoy O Murry JB Machini K Lebo MS Yu TW Fayer S Interpretation of genomic sequencing results in healthy and Ill newborns: results from the BabySeq Project Am J Hum Genet 2019 104 76 93 30609409 PMC6323417
  69. [77]Lord CJ Tutt A Ashworth A Synthetic lethality and cancer therapy: lessons learned from the development of PARP inhibitors Annu Rev Med 2015 66 455 70 25341009
  70. [78]DeBoever C Tanigawa Y Aguirre M McInnes G Lavertu A Rivas MA Assessing digital phenotyping to enhance genetic studies of human diseases Am J Hum Genet 2020 106 611 22 32275883 PMC7212271
  71. [79]Shendure J Balasubramanian S Church GM Gilbert W Rogers J Schloss JA DNA sequencing at 40: past, present and future Nature. 2017 550 345 53 29019985
  72. [80]Zhang D Zhao L Li B He Z Wang GT Liu DJ SEQSpark: a complete analysis tool for large-scale rare variant association studies using whole-genome and exome sequence data Am J Hum Genet 2017 101 115 22 28669402 PMC5501866
  73. [82]Weitzel JN Chao EC Nehoray B Tongeren LR LaDuca H Blazer KR Somatic TP53 variants frequently confound germ-line testing results Genet Med 2018 20 809 16 29189820 PMC5976505
  74. [83]Pharoah PDP Song H Dicks E Intermaggio MP Harrington P Baynes C PPM1D Mosaic truncating variants in ovarian cancer cases may be treatment-related somatic mutations J Natl Cancer Inst 2016 108 djv347 PMC5072371 26823519
  75. [84]Sazonovs A Barrett JC Rare-variant studies to complement genome-wide association studies Annu Rev Genom Hum Genet 2018 19 97 112 29801418
  76. [86]Ioannidis JPA Tarone R McLaughlin JK The false-positive to false-negative ratio in epidemiologic studies Epidemiology. 2011 22 450 56 21490505
  77. [88]Suzuki K Akiyama M Ishigaki K Kanai M Hosoe J Shojima N Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population Nat Genet 2019 51 379 86 30718926
  78. [89]Wojcik GL Graff M Nishimura KK Tao R Haessler J Gignoux CR Genetic analyses of diverse populations improves discovery for complex traits Nature. 2019 570 514 18 31217584 PMC6785182
  79. [90]Minikel E Karczewski KJ Martin HC Cummings BB Whiffin N Rhodes D Evaluating drug targets through human loss-of-function genetic variation Nature. 2020 581 459 64 32461653 PMC7272226
  80. [91]Cummings BB Karczewski KJ Kosmicki JA Seaby EG Watts NA Singer-Berk M Transcript expression-aware annotation improves rare variant interpretation Nature. 2020 581 452 58 32461655 PMC7334198
  81. [92]Mahmood K Jung C-H Philip G Georgeson P Chung J Pope BJ Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics Hum Genom 2017 11 10 PMC5433009 28511696
  82. [93]Findlay GM Daza RM Martin B Zhang MD Leith AP Gasperini M Accurate classification of BRCA1 variants with saturation genome editing Nature. 2018 562 217 22 30209399 PMC6181777
  83. [94]Kuiper RP Vissers L Venkatachalam R Bodmer D Hoenselaar E Goossens M Recurrence and variability of germline EPCAM deletions in Lynch syndrome Hum Mutat 2011 32 407 14 21309036
  84. [95]Hernandez RD Uricchio LH Hartman K Ye C Dahl A Zaitlen N Ultrarare variants drive substantial cis heritability of human gene expression Nat Genet 2019 51 1349 55 31477931 PMC6730564
  85. [96]Evans DGR van Veen EM Byers HJ Wallace AJ Ellingford JM Beaman G A dominantly inherited 5′ UTR variant causing methylation-associated silencing of BRCA1 as a cause of breast and ovarian cancer Am J Hum Genet 2018 103 213 20 30075112 PMC6080768
  86. [97]Ye Y Zhang Z Liu Y Diao L Han L A multi-omics perspective of quantitative trait loci in precision medicine Trends Genet 2020 36 318 36 32294413
  87. [98]Fulco CP Nasser J Jones TR Munson G Bergman DT Subramanian V Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations Nat Genet 2019 51 1664 69 31784727 PMC6886585
  88. [99]Zhang S He Y Liu H Zhai H Huang D Yi X regBase: whole genome base-wise aggregation and functional prediction for human non-coding regulatory variants Nucleic Acids Res 2019 47 e134 31511901 PMC6868349
  89. [100]Lin H Hargreaves KA Li R Reiter JL Wang Y Mort M RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants Genome Biol 2019 20 254 31779641 PMC6883696
  90. [101]Lou S Cotter KA Li T Liang J Mohsen H Liu J GRAM: A GeneRAlized Model to predict the molecular effect of a non-coding variant in a cell-type specific manner PLoS Genet 2019 15 e1007860 31469829 PMC6742416
  91. [102]Collins RL Brand H Karczewski KJ Zhao X Alföldi J Francioli L A structural variation reference for medical and population genetics Nature. 2020 581 444 51 32461652 PMC7334194
  92. [103]Dias R Torkamani A Artificial intelligence in clinical and genomic diagnostics Genome Med 2019 11 70 31744524 PMC6865045
  93. [104]Diogo D Kurreeman F Stahl EA Liao KP Gupta N Greenberg JD Rare, low-frequency, and common variants in the protein-coding sequence of biological candidate genes from GWASs contribute to risk of rheumatoid arthritis Am J Hum Genet 2013 92 15 27 23261300 PMC3542467
  94. [105]Seddon JM Yu Y Miller EC Reynolds R Tan PL Gowrisankar S Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration Nat Genet 2013 45 1366 70 24036952 PMC3902040
  95. [109]Singh T Kurki MI Curtis D Purcell SM Crooks L McRae J Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders Nat Neurosci 2016 19 571 77 26974950 PMC6689268
  96. [110]Momozawa Y Akiyama M Kamatani Y Arakawa S Yasuda M Yoshida S Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population Hum Mol Genet 2016 25 5027 34 28173125
  97. [112]Choi S Weng L-C Roselli C Lin H Haggerty CM Shoemaker BM Association between titin loss-of-function variants and early-onset atrial fibrillation JAMA. 2018 320 2354 64 30535219 PMC6436530
  98. [113]Dressen A Abbas AR Cabanski C Reeder J Ramalingam TR Neighbors M Analysis of protein-altering variants in telomerase genes and their association with MUC5B common variant status in patients with idiopathic pulmonary fibrosis: a candidate gene sequencing study Lancet Respir Med. 2018 6 603 14 29891356 PMC6487850
  99. [115]Cochran NJ Geier EG Bonham LW Newberry SJ Amaral MD Thompson ML Non-coding and loss-of-function coding variants in TET2 are associated with multiple neurodegenerative diseases Am J Hum Genet 2020 106 632 45 32330418 PMC7212268
  100. [116]Hamilton PJ Campbell NG Sharma S Erreger K Hansen HF Saunders C De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder Mol Psychiatry 2013 18 1315 23 23979605 PMC4046646
  101. [117]Steri M Orrù V Idda LM Pitzalis M Pala M Zara I Overexpression of the cytokine BAFF and autoimmunity risk N Engl J Med 2017 376 1615 26 28445677 PMC5605835
  102. [118]Chang J Zhong R Tian J Li J Zhai K Ke J Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma Nat Genet 2018 50 338 43 29379198
  103. [119]Nissim S Leshchiner I Mancias JD Greenblatt MB Maertens O Cassa CA Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer Nat Genet 2019 51 1308 14 31406347 PMC7159804
  104. [120]Jiang SH Athanasopoulos V Ellyard JI Chuah A Cappello J Cook A Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus Nat Commun 2019 10 2201 31101814 PMC6525203
  105. [121]Dwivedi O Lehtovirta M Hastoy B Chandra V Krentz NAJ Kleiner S Loss of ZnT8 function protects against diabetes by enhanced insulin secretion Nat Genet 2019 51 1596 606 31676859 PMC6858874
  106. [122]Tolosa E Vila M Klein C Rascol O LRRK2 in Parkinson disease: challenges of clinical trials Nat Rev Neurol 2020 16 97 107 31980808
  107. [123]Whiffin N, Armean IM, Kleinman A, Marshall JL, Minikel EV, Goodrich JK, et al. The effect of LRRK2 loss-of-function variants in humans. Nat Med. 2020;26:869–77. PMC7303015 32461697
  108. [124]Wang X-J, Xu X-Q, Sun K, Liu K-Q, Li S-Q, Jiang X, et al. Association of rare PTGIS variants with susceptibility and pulmonary vascular response in patients with idiopathic pulmonary arterial hypertension. JAMA Cardiol. 2020;5:677–84. PMC7113838 32236489
  109. [126]Singh D Cadden P Hunter M Collins L Perkins M Pettipher R Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459 Eur Respir J 2012 41 46 52 22496329
  110. [127]Kaufman B Shapira-Frommer R Schmutzler RK Audeh WM Friedlander M Balmaña J Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation J Clin Oncol 2015 33 244 50 25366685 PMC6057749
  111. [128]Goldberg YP Pimstone SN Namdari R Price N Cohen C Sherrington RP Human Mendelian pain disorders: a key to discovery and validation of novel analgesics Clin Genet 2012 82 367 73 22845492
  112. [129]Sabatine MS PCSK9 inhibitors: clinical evidence and implementation Nat Rev Cardiol 2019 16 155 65 30420622
  113. [130]Hall J Dennler P Haller S Pratsinis A Säuberli K Towbin H Genomics drugs in clinical trials Nat Rev Drug Discov 2010 9 988 21119735

Cited by

Sorted by citations

Authors
Momozawa, Y., & Mizukami, K.
Affiliations
RIKEN Center for Integrative Medical Sciences (JP)
Corresponding author
Momozawa, Yukihide
ORCID
Venue
Journal of Human Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-09-18
Volume
66
Issue
1
Pages
11-23
ISSN
  • 1434-5161 (ISSN-L)
  • 1435-232X
DOI
10.1038/s10038-020-00845-2
PMC
PMC7728599
OpenAlex
W3087433133
Cited by
161
References
17
Citations by year
2026: 26 · 2025: 34 · 2024: 43 · 2023: 17 · 2022: 24 · 2021: 17
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Human Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Japan Agency for Medical Research and Development (JP20ck0106402, JP19cm0106605)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
rare variants, complex diseases, common genetic variants, imputation, disease mechanisms, drug discovery targets, genetic risk markers, personalized medicine, functional impact of variants
MeSH terms
Whole Genome Sequencing, Gene Frequency, Genotype, Humans, Genetic Variation, Genome, Human, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Precision Medicine

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