Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Cell

Volumn 167, Issue 5, 2016, Pages 1398-1414.e24

  Chen, Lu ^a,b   Ge, Bing ^c   Casale, Francesco Paolo ^d   Vasquez, Louella ^a   Kwan, Tony ^c   Garrido Martín, Diego ^e,f   Watt, Stephen ^a   Yan, Ying ^a   Kundu, Kousik ^a,b   Ecker, Simone ^g,h   Datta, Avik ⁱ   Richardson, David ⁱ   Burden, Frances ^b,o   Mead, Daniel ^a   Mann, Alice L ^a   Fernandez, Jose Maria ^g   Rowlston, Sophia ^b,o   Wilder, Steven P ⁱ   Farrow, Samantha ^b,o   Shao, Xiaojian ^c   Lambourne, John J ^b,c,o   Redensek, Adriana ^c   Albers, Cornelis A ^k,n   Amstislavskiy, Vyacheslav ^l   Ashford, Sofie ^b,o   Berentsen, Kim ^m   Bomba, Lorenzo ^a   Bourque, Guillaume ^c   Bujold, David ^c   Busche, Stephan ^c   Caron, Maxime ^c   Chen, Shu Huang ^c   Cheung, Warren ^c   Delaneau, Oliver ^j   Dermitzakis, Emmanouil T ^j   Elding, Heather ^a   Colgiu, Irina ⁱ   Bagger, Frederik O ^b,d,o   Flicek, Paul ⁱ   Habibi, Ehsan ^m   Iotchkova, Valentina ^a   Janssen Megens, Eva ^m   Kim, Bowon ^m   Lehrach, Hans ^l   Lowy, Ernesto ⁱ   Mandoli, Amit ^m   Matarese, Filomena ^m   Maurano, Matthew T ^p   Morris, John A ^c   Pancaldi, Vera ^g   Pourfarzad, Farzin ^q   Rehnstrom, Karola ^b,o   Rendon, Augusto ^b,r   Risch, Thomas ^l   Sharifi, Nilofar ^m   Simon, Marie Michelle ^c   Sultan, Marc ^l   Valencia, Alfonso ^g   Walter, Klaudia ^a   Wang, Shuang Yin ^m   Frontini, Mattia ^b,o,s   Antonarakis, Stylianos E ^j   Clarke, Laura ⁱ   Yaspo, Marie Laure ^l   Beck, Stephan ^h   Guigo, Roderic ^e,f,t   Rico, Daniel ^g,u   Martens, Joost H A ^m   Ouwehand, Willem H ^a,b,o,s,v   Kuijpers, Taco W ^b,q,w   Paul, Dirk S ^h,x   Stunnenberg, Hendrik G ^m   Stegle, Oliver ^d   Downes, Kate ^b,o   Pastinen, Tomi ^c   Soranzo, Nicole ^a,b,s,v   more..

^a WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c MCGILL UNIVERSITY   (Canada)

^d EUROPEAN BIOINFORMATICS INSTITUTE   (United Kingdom)

^e CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^f UNIVERSITAT POMPEU FABRA   (Spain)

^g Centro Nacional de Investigaciones Oncológicas   (United Kingdom)

^h UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁱ WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^j UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

^k RADBOUD UNIVERSITY   (Netherlands)

^l MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS   (Germany)

^m RADBOUD UNIVERSITY NIJMEGEN   (Netherlands)

ⁿ RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^o NHS BLOOD AND TRANSPLANT   (United Kingdom)

^p NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^q Sanquin Research and Landsteiner Laboratory   (United Kingdom)

^r GENOMICS ENGLAND   (United Kingdom)

^s ADDENBROOKE S HOSPITAL   (United Kingdom)

^t Institut Hospital del Mar d'Investigacions Mediques (IMIM)   (United Kingdom)

^u NEWCASTLE UNIVERSITY   (United Kingdom)

^v University of Amsterdam ^*  (United Kingdom)

^w UNIVERSITY OF AMSTERDAM   (Netherlands)

^x UNIVERSITY OF CAMBRIDGE   (United Kingdom)

more..

Author keywords

allele specific; DNA methylation; EWAS; histone modification; immune; monocyte; neutrophil; QTL; t cell; transription

Indexed keywords

CD14 ANTIGEN; HISTONE;

ALLELE; ALTERNATIVE RNA SPLICING; ARTICLE; CD4+ T LYMPHOCYTE; EPIGENETICS; GENE EXPRESSION; GENETIC REGULATION; GENOME-WIDE ASSOCIATION STUDY; HISTONE MODIFICATION; HUMAN; HUMAN CELL; IMMUNOCOMPETENT CELL; METHYLATION; MOLECULAR DYNAMICS; MONOCYTE; NEUTROPHIL; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; QUANTITATIVE TRAIT LOCUS MAPPING; RNA SEQUENCE; TRANSCRIPTION REGULATION; TRANSCRIPTOMICS; ADULT; AGED; FEMALE; GENETIC PREDISPOSITION; GENETIC TRANSCRIPTION; GENETICS; HEMATOPOIETIC STEM CELL; HISTONE CODE; IMMUNOPATHOLOGY; MALE; METABOLISM; MIDDLE AGED; QUANTITATIVE TRAIT LOCUS; T LYMPHOCYTE; YOUNG ADULT;

ADULT; AGED; ALTERNATIVE SPLICING; EPIGENOMICS; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HEMATOPOIETIC STEM CELLS; HISTONE CODE; HUMANS; IMMUNE SYSTEM DISEASES; MALE; MIDDLE AGED; MONOCYTES; NEUTROPHILS; QUANTITATIVE TRAIT LOCI; T-LYMPHOCYTES; TRANSCRIPTION, GENETIC; YOUNG ADULT;

EID: 84995752772     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2016.10.026     Document Type: Article

References (70)

1. Abnizova, I., Skelly, T., Naumenko, F., Whiteford, N., Brown, C., Cox, T., Statistical comparison of methods to estimate the error probability in short-read Illumina sequencing. J. Bioinform. Comput. Biol. 8 (2010), 579–591.
2. Adoue, V., Schiavi, A., Light, N., Almlöf, J.C., Lundmark, P., Ge, B., Kwan, T., Caron, M., Rönnblom, L., Wang, C., et al. Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs. Mol. Syst. Biol., 10, 2014, 754.
3. Aldridge, S., Watt, S., Quail, M.A., Rayner, T., Lukk, M., Bimson, M.F., Gaffney, D., Odom, D.T., AHT-ChIP-seq: a completely automated robotic protocol for high-throughput chromatin immunoprecipitation. Genome Biol., 14, 2013, R124.
4. Allum, F., Shao, X., Guénard, F., Simon, M.M., Busche, S., Caron, M., Lambourne, J., Lessard, J., Tandre, K., Hedman, A.K., et al., Multiple Tissue Human Expression Resource Consortium. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants. Nat. Commun., 6, 2015, 7211.
5. Anderson, C.A., Boucher, G., Lees, C.W., Franke, A., D'Amato, M., Taylor, K.D., Lee, J.C., Goyette, P., Imielinski, M., Latiano, A., et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43 (2011), 246–252.
6. Aryee, M.J., Jaffe, A.E., Corrada-Bravo, H., Ladd-Acosta, C., Feinberg, A.P., Hansen, K.D., Irizarry, R.A., Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30 (2014), 1363–1369.
7. Battle, A., Mostafavi, S., Zhu, X., Potash, J.B., Weissman, M.M., McCormick, C., Haudenschild, C.D., Beckman, K.B., Shi, J., Mei, R., et al. Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res. 24 (2014), 14–24.
8. Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., et al. International Multiple Sclerosis Genetics Consortium (IMSGC) Wellcome Trust Case Control Consortium 2 (WTCCC2), International IBD Genetics Consortium (IIBDGC). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 45 (2013), 1353–1360.
9. Bentham, J., Morris, D.L., Cunninghame Graham, D.S., Pinder, C.L., Tombleson, P., Behrens, T.W., Martín, J., Fairfax, B.P., Knight, J.C., Chen, L., et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat. Genet. 47 (2015), 1457–1464.
10. Browning, S.R., Browning, B.L., Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J. Hum. Genet. 81 (2007), 1084–1097.
11. Carrillo de Santa Pau, E., Juan, D., Pancaldi, V., Were, F., Martin-Subero, I., Rico, D., Valencia, A., Searching for the chromatin determinants of human hematopoiesis. bioRxiv, 2016, 10.1101/082917.
12. Casale, F.P., Rakitsch, B., Lippert, C., Stegle, O., Efficient set tests for the genetic analysis of correlated traits. Nat. Methods 12 (2015), 755–758.
13. Chen, C., Grennan, K., Badner, J., Zhang, D., Gershon, E., Jin, L., Liu, C., Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. PLoS ONE, 6, 2011, e17238.
14. Chen, L., Kostadima, M., Martens, J.H., Canu, G., Garcia, S.P., Turro, E., Downes, K., Macaulay, I.C., Bielczyk-Maczynska, E., Coe, S., et al., BRIDGE Consortium. Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345, 2014, 1251033.
15. DePristo, M.A., Banks, E., Poplin, R., Garimella, K.V., Maguire, J.R., Hartl, C., Philippakis, A.A., del Angel, G., Rivas, M.A., Hanna, M., et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43 (2011), 491–498.
16. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., Gingeras, T.R., STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 (2013), 15–21.
17. Dubois, P.C., Trynka, G., Franke, L., Hunt, K.A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G.A., Adány, R., Aromaa, A., et al. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42 (2010), 295–302.
18. Ernst, J., Kellis, M., ChromHMM: automating chromatin-state discovery and characterization. Nat. Methods 9 (2012), 215–216.
19. Fairfax, B.P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C., Knight, J.C., Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science, 343, 2014, 1246949.
20. Farh, K.K., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W.J., Beik, S., Shoresh, N., Whitton, H., Ryan, R.J., Shishkin, A.A., et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518 (2015), 337–343.
21. Foissac, S., Sammeth, M., ASTALAVISTA: dynamic and flexible analysis of alternative splicing events in custom gene datasets. Nucleic Acids Res. 35 (2007), W297–W299.
22. Ge, B., Pokholok, D.K., Kwan, T., Grundberg, E., Morcos, L., Verlaan, D.J., Le, J., Koka, V., Lam, K.C., Gagné, V., et al. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis. Nat. Genet. 41 (2009), 1216–1222.
23. Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., Plagnol, V., Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet., 10, 2014, e1004383.
24. Grubert, F., Zaugg, J.B., Kasowski, M., Ursu, O., Spacek, D.V., Martin, A.R., Greenside, P., Srivas, R., Phanstiel, D.H., Pekowska, A., et al. Genetic control of chromatin states in humans involves local and distal chromosomal interactions. Cell 162 (2015), 1051–1065.
25. Gurdasani, D., Carstensen, T., Tekola-Ayele, F., Pagani, L., Tachmazidou, I., Hatzikotoulas, K., Karthikeyan, S., Iles, L., Pollard, M.O., Choudhury, A., et al. The African Genome Variation Project shapes medical genetics in Africa. Nature 517 (2015), 327–332.
26. Gutierrez-Arcelus, M., Lappalainen, T., Montgomery, S.B., Buil, A., Ongen, H., Yurovsky, A., Bryois, J., Giger, T., Romano, L., Planchon, A., et al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation. eLife, 2, 2013, e00523.
27. Harrow, J., Frankish, A., Gonzalez, J.M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B.L., Barrell, D., Zadissa, A., Searle, S., et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22 (2012), 1760–1774.
28. Hindorff, L.A., Sethupathy, P., Junkins, H.A., Ramos, E.M., Mehta, J.P., Collins, F.S., Manolio, T.A., Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106 (2009), 9362–9367.
29. Horvath, S., DNA methylation age of human tissues and cell types. Genome Biol., 14, 2013, R115.
30. Iotchkova, V., Ritchie, G.R.S., Geihs, M., Morganella, S., Min, J.L., Walter, K., Timpson, N.J. UK10K Consortium, Dunham, I., Birney, E., Nicole Soranzo, GARFIELD - GWAS Analysis of Regulatory or Functional Information Enrichment with LD correction. bioRxiv, 2016, 10.1101/085738.
31. Johnson, W.E., Li, C., Rabinovic, A., Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8 (2007), 118–127.
32. Jostins, L., Ripke, S., Weersma, R.K., Duerr, R.H., McGovern, D.P., Hui, K.Y., Lee, J.C., Schumm, L.P., Sharma, Y., Anderson, C.A., et al., International IBD Genetics Consortium (IIBDGC). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491 (2012), 119–124.
33. Kang, H.M., Ye, C., Eskin, E., Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots. Genetics 180 (2008), 1909–1925.
34. Kang, H.M., Zaitlen, N.A., Wade, C.M., Kirby, A., Heckerman, D., Daly, M.J., Eskin, E., Efficient control of population structure in model organism association mapping. Genetics 178 (2008), 1709–1723.
35. Kumasaka, N., Knights, A.J., Gaffney, D.J., Fine-mapping cellular QTLs with RASQUAL and ATAC-seq. Nat. Genet. 48 (2016), 206–213.
36. Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., Ziller, M.J., et al., Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature 518 (2015), 317–330.
37. Lee, S.H., Goddard, M.E., Visscher, P.M., van der Werf, J.H., Using the realized relationship matrix to disentangle confounding factors for the estimation of genetic variance components of complex traits. Genet. Sel. Evol., 42, 2010, 22.
38. Leek, J.T., Johnson, W.E., Parker, H.S., Jaffe, A.E., Storey, J.D., The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28 (2012), 882–883.
39. Li, H., A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 27 (2011), 2987–2993.
40. Li, H., Durbin, R., Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25 (2009), 1754–1760.
41. Li, Y.I., van de Geijn, B., Raj, A., Knowles, D.A., Petti, A.A., Golan, D., Gilad, Y., Pritchard, J.K., RNA splicing is a primary link between genetic variation and disease. Science 352 (2016), 600–604.
42. Lippert, C., Casale, F.P., Rakitsch, B., Stegle, O., LIMIX: genetic analysis of multiple traits. bioRxiv, 2014, 10.1101/003905.
43. Liu, J.Z., van Sommeren, S., Huang, H., Ng, S.C., Alberts, R., Takahashi, A., Ripke, S., Lee, J.C., Jostins, L., Shah, T., et al. International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47 (2015), 979–986.
44. Love, M.I., Huber, W., Anders, S., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 2014, 550.
45. Maksimovic, J., Gordon, L., Oshlack, A., SWAN: Subset-quantile within array normalization for illumina infinium HumanMethylation450 BeadChips. Genome Biol., 13, 2012, R44.
46. Melcher, M., Unger, B., Schmidt, U., Rajantie, I.A., Alitalo, K., Ellmeier, W., Essential roles for the Tec family kinases Tec and Btk in M-CSF receptor signaling pathways that regulate macrophage survival. J. Immunol. 180 (2008), 8048–8056.
47. Monlong, J., Calvo, M., Ferreira, P.G., Guigó, R., Identification of genetic variants associated with alternative splicing using sQTLseekeR. Nat. Commun., 5, 2014, 4698.
48. Montgomery, S.B., Dermitzakis, E.T., From expression QTLs to personalized transcriptomics. Nat. Rev. Genet. 12 (2011), 277–282.
49. Morales, J.L., Nocedal, J., Remark on Algorithm 778: L-BFGS-B, FORTRAN routines for large scale bound constrained optimization. ACM Trans. Math. Softw., 38, 2011, 1.
50. Morris, A.P., Voight, B.F., Teslovich, T.M., Ferreira, T., Segrè, A.V., Steinthorsdottir, V., Strawbridge, R.J., Khan, H., Grallert, H., Mahajan, A., et al. Wellcome Trust Case Control Consortium Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators Genetic Investigation of ANthropometric Traits (GIANT) Consortium Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium South Asian Type 2 Diabetes (SAT2D) Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44 (2012), 981–990.
51. Naranbhai, V., Fairfax, B.P., Makino, S., Humburg, P., Wong, D., Ng, E., Hill, A.V., Knight, J.C., Genomic modulators of gene expression in human neutrophils. Nat. Commun., 6, 2015, 7545.
52. Nica, A.C., Parts, L., Glass, D., Nisbet, J., Barrett, A., Sekowska, M., Travers, M., Potter, S., Grundberg, E., Small, K., et al., MuTHER Consortium. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet., 7, 2011, e1002003.
53. Nordlund, J., Bäcklin, C.L., Wahlberg, P., Busche, S., Berglund, E.C., Eloranta, M.L., Flaegstad, T., Forestier, E., Frost, B.M., Harila-Saari, A., et al. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biol., 14, 2013, r105.
54. Okada, Y., Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., Suzuki, A., Yoshida, S., et al. RACI consortium, GARNET consortium. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506 (2014), 376–381.
55. Onengut-Gumuscu, S., Chen, W.M., Burren, O., Cooper, N.J., Quinlan, A.R., Mychaleckyj, J.C., Farber, E., Bonnie, J.K., Szpak, M., Schofield, E., et al., Type 1 Diabetes Genetics Consortium. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat. Genet. 47 (2015), 381–386.
56. Ong, C.T., Corces, V.G., Enhancers: emerging roles in cell fate specification. EMBO Rep. 13 (2012), 423–430.
57. Pastinen, T., Genome-wide allele-specific analysis: insights into regulatory variation. Nat. Rev. Genet. 11 (2010), 533–538.
58. Pickrell, J.K., Berisa, T., Liu, J.Z., Ségurel, L., Tung, J.Y., Hinds, D.A., Detection and interpretation of shared genetic influences on 42 human traits. Nat. Genet. 48 (2016), 709–717.
59. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., Sham, P.C., PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81 (2007), 559–575.
60. Schmidt, U., Boucheron, N., Unger, B., Ellmeier, W., The role of Tec family kinases in myeloid cells. Int. Arch. Allergy Immunol. 134 (2004), 65–78.
61. Stegle, O., Parts, L., Piipari, M., Winn, J., Durbin, R., Using probabilistic estimation of expression residuals (PEER) to obtain increased power and interpretability of gene expression analyses. Nat. Protoc. 7 (2012), 500–507.
62. Storey, J.D., Tibshirani, R., Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100 (2003), 9440–9445.
63. Trapnell, C., Williams, B.A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M.J., Salzberg, S.L., Wold, B.J., Pachter, L., Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28 (2010), 511–515.
64. Triche, T.J. Jr., Weisenberger, D.J., Van Den Berg, D., Laird, P.W., Siegmund, K.D., Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res., 41, 2013, e90.
65. van de Geijn, B., McVicker, G., Gilad, Y., Pritchard, J.K., WASP: allele-specific software for robust molecular quantitative trait locus discovery. Nat. Methods 12 (2015), 1061–1063.
66. Waszak, S.M., Delaneau, O., Gschwind, A.R., Kilpinen, H., Raghav, S.K., Witwicki, R.M., Orioli, A., Wiederkehr, M., Panousis, N.I., Yurovsky, A., et al. Population variation and genetic control of modular chromatin architecture in humans. Cell 162 (2015), 1039–1050.
67. Welter, D., MacArthur, J., Morales, J., Burdett, T., Hall, P., Junkins, H., Klemm, A., Flicek, P., Manolio, T., Hindorff, L., Parkinson, H., The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42 (2014), D1001–D1006.
68. Wong, J.J., Ritchie, W., Ebner, O.A., Selbach, M., Wong, J.W., Huang, Y., Gao, D., Pinello, N., Gonzalez, M., Baidya, K., et al. Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154 (2013), 583–595.
69. Yang, J., Lee, S.H., Goddard, M.E., Visscher, P.M., GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88 (2011), 76–82.
70. Zhang, Y., Liu, T., Meyer, C.A., Eeckhoute, J., Johnson, D.S., Bernstein, B.E., Nusbaum, C., Myers, R.M., Brown, M., Li, W., Liu, X.S., Model-based analysis of ChIP-Seq (MACS). Genome Biol., 9, 2008, R137.