Massively parallel quantification of the regulatory effects of noncoding genetic variation in a human cohort

Genome Research

Volumn 25, Issue 8, 2015, Pages 1206-1214

  Vockley, Christopher M ^a   Guo, Cong ^a,b   Majoros, William H ^a,b   Nodzenski, Michael ^c   Scholtens, Denise M ^c   Hayes, M Geoffrey ^c   Lowe, William L ^c   Reddy, Timothy E ^a,b  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b DUKE UNIVERSITY   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; MESSENGER RNA;

3' UNTRANSLATED REGION; ARTICLE; COHORT ANALYSIS; GENE CONTROL; GENE EXPRESSION ASSAY; GENE FREQUENCY; GENE MAPPING; GENETIC ASSOCIATION; GENETIC TRANSFECTION; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; HAPLOTYPE; HEPG2 CELL LINE; HIGH THROUGHPUT SEQUENCING; HOST CELL; HUMAN; HUMAN CELL; MULTIPLEX POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RNA SEQUENCE; SEQUENCE ALIGNMENT; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTION INITIATION SITE; BIOLOGICAL MODEL; BIOLOGY; GENETIC VARIATION; HUMAN GENOME; PROCEDURES; QUANTITATIVE TRAIT LOCUS; REGULATORY SEQUENCE;

COMPUTATIONAL BIOLOGY; GENETIC VARIATION; GENOME, HUMAN; HAPLOTYPES; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; PATIENT-SPECIFIC MODELING; QUANTITATIVE TRAIT LOCI; REGULATORY SEQUENCES, NUCLEIC ACID;

EID: 84938876935     PISSN: 10889051     EISSN: 15495469     Source Type: Journal    
DOI: 10.1101/gr.190090.115     Document Type: Article

References (53)

1. The 1000 Genomes Project Consortium. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56-65.
2. Arnold CD, Gerlach D, Stelzer C, Boryń LM, Rath M, Stark A. 2013. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339: 1074-1077.
3. Battle A, Mostafavi S, Zhu X, Potash JB, Weissman MM, McCormick C, Haudenschild CD, Beckman KB, Shi J, Mei R, et al. 2014. Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res 24: 14-24.
4. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57: 289-300.
5. Birney E, Lieb JD, Furey TS, Crawford GE, Iyer VR. 2010. Allele-specific and heritable chromatin signatures in humans. Hum Mol Genet 19: R204-R209.
6. Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AF, Roskin KM, Baertsch R, Rosenbloom K, Clawson H, Green ED, et al. 2004. Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res 14: 708-715.
7. Cantor RM, Lange K, Sinsheimer JS. 2010. Prioritizing GWAS results: a review of statistical methods and recommendations for their application. Am J Hum Genet 86: 6-22.
8. Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. 2012. Predicting the functional effect of amino acid substitutions and indels. PLoS One 7: e46688.
9. Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J, Cowper-Sal-lari R, Lupien M, Markowitz S, Scacheri PC. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 24: 1-13.
10. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA, et al. 2010. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci 107: 21931-21936.
11. Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ, Pickrell JK, De Leon S, Michelini K, Lewellen N, Crawford GE, et al. 2012. DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482: 390-394.
12. Delaneau O, Marchini J, Zagury JF. 2012. A linear complexity phasing method for thousands of genomes. Nat Methods 9: 179-181.
13. Delaneau O, Howie B, Cox AJ, Zagury JF, Marchini J. 2013a. Haplotype estimation using sequencing reads. Am J Hum Genet 93: 687-696.
14. Delaneau O, Zagury JF, Marchini J. 2013b. Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 10: 5-6.
15. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, et al. 2011. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43: 491-498.
16. The ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74.
17. Ernst J, Kellis M. 2012. ChromHMM: automating chromatin-state discovery and characterization. Nat Methods 9: 215-216.
18. Feng Q, Vickers KC, Anderson MP, Levin MG, Chen W, Harrison DG, Wilke RA. 2013. A common functional promoter variant links CNR1 gene expression to HDL cholesterol level. Nat Commun 4: 1973.
19. Fogarty MP, Cannon ME, Vadlamudi S, Gaulton KJ, Mohlke KL. 2014. Identification of a regulatory variant that binds FOXA1 and FOXA2 at the CDC123/CAMK1D type 2 diabetes GWAS locus. PLoS Genet 10: e1004633.
20. Gisselbrecht SS, Barrera LA, Porsch M, Aboukhalil A, Estep PW III, Vedenko A, Palagi A, Kim Y, Zhu X, Busser BW, et al. 2013. Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos. Nat Methods 10: 774-780.
21. Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, Brown CD, Newgard CB, Becker TC, Layden BT, et al. 2015. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun 6: 6069.
22. Gusev A, Lee SH, Trynka G, Finucane H, Vilhjálmsson BJ, Xu H, Zang C, Ripke S, Bulik-Sullivan B, Stahl E, et al. 2014. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am J Hum Genet 95: 535-552.
23. Hu H, Huff CD, Moore B, Flygare S, Reese MG, Yandell M. 2013. VAAST 2.0: improved variant classification and disease-gene identification using a conservation-controlled amino acid substitution matrix. Genet Epidemiol 37: 622-634.
24. Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. 2002. The human genome browser at UCSC. Genome Res 12: 996-1006.
25. Kilpinen H, Waszak SM, Gschwind AR, Raghav SK, Witwicki RM, Orioli A, Migliavacca E, Wiederkehr M, Gutierrez-Arcelus M, Panousis NI, et al. 2013. Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription. Science 342: 744-747.
26. Kwasnieski JC, Mogno I, Myers CA, Corbo JC, Cohen BA. 2012. Complex effects of nucleotide variants in a mammalian cis-regulatory element. Proc Natl Acad Sci 109: 19498-19503.
27. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357-359.
28. Lappalainen T, Sammeth M, Friedländer MR, 't Hoen PA, Monlong J, Rivas MA, Gonzàlez-Porta M, Kurbatova N, Griebel T, Ferreira PG, et al. 2013. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501: 506-511.
29. Li B, Leal SM. 2008. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet 83: 311-321.
30. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Genome Project Data Processing S. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078-2079.
31. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J, et al. 2012. Systematic localization of common disease-associated variation in regulatory DNA. Science 337: 1190-1195.
32. McDaniell R, Lee BK, Song L, Liu Z, Boyle AP, Erdos MR, Scott LJ, Morken MA, Kucera KS, Battenhouse A, et al. 2010. Heritable individual-specific and allele-specific chromatin signatures in humans. Science 328: 235-239.
33. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, et al. 2010. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297-1303.
34. Melnikov A, Murugan A, Zhang X, Tesileanu T, Wang L, Rogov P, Feizi S, Gnirke A, Callan CG Jr, Kinney JB, et al. 2012. Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat Biotechnol 30: 271-277.
35. Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ. 2010. Traitassociated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet 6: e1000888.
36. O'Connell J, Gurdasani D, Delaneau O, Pirastu N, Ulivi S, Cocca M, Traglia M, Huang J, Huffman JE, Rudan I, et al. 2014. A general approach for haplotype phasing across the full spectrum of relatedness. PLoS Genet 10: e1004234.
37. Olansky L, Welling C, Giddings S, Adler S, Bourey R, Dowse G, Serjeantson S, Zimmet P, Permutt MA. 1992. A variant insulin promoter in non-insulin-dependent diabetes mellitus. J Clin Invest 89: 1596-1602.
38. Patwardhan RP, Lee C, Litvin O, Young DL, Pe'er D, Shendure J. 2009. Highresolution analysis of DNA regulatory elements by synthetic saturation mutagenesis. Nat Biotechnol 27: 1173-1175.
39. Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, et al. 2012. Massively parallel functional dissection of mammalian enhancers in vivo. Nat Biotechnol 30: 265-270.
40. Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, et al. 2006. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444: 499-502.
41. Quinlan AR, Hall IM. 2010. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841-842.
42. R Core Team. 2015. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.Rproject.org/.
43. Reddy TE, Gertz J, Pauli F, Kucera KS, Varley KE, Newberry KM, Marinov GK, Mortazavi A, Williams BA, Song L, et al. 2012. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression. Genome Res 22: 860-869.
44. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. 2001. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29: 308-311.
45. Shlyueva D, Stelzer C, Gerlach D, Yáñez-Cuna JO, Rath M, Boryń LM, Arnold CD, Stark A. 2014. Hormone-responsive enhancer-activity maps reveal predictive motifs, indirect repression, and targeting of closed chromatin. Mol Cell 54: 180-192.
46. Stadhouders R, Aktuna S, Thongjuea S, Aghajanirefah A, Pourfarzad F, van Ijcken W, Lenhard B, Rooks H, Best S, Menzel S, et al. 2014. HBS1LMYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. J Clin Invest 124: 1699-1710.
47. Stegle O, Parts L, Durbin R, Winn J. 2010. A Bayesian framework to account for complex non-genetic factors in gene expression levels greatly increases power in eQTL studies. PLoS Comput Biol 6: e1000770.
48. Stranger BE, Raj T. 2013. Genetics of human gene expression. Curr Opin Genet Dev 23: 627-634.
49. Urbanek M, Hayes MG, Armstrong LL, Morrison J, Lowe LP, Badon SE, Scheftner D, Pluzhnikov A, Levine D, Laurie CC, et al. 2013. The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study. Hum Mol Genet 22: 3583-3596.
50. Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, et al. 2013. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics 11: 11 10 11-11 10 33.
51. White MA, Myers CA, Corbo JC, Cohen BA. 2013. Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. Proc Natl Acad Sci 110: 11952-11957.
52. Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, Stark A. 2015. Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature 518: 556-559.
53. Zawistowski M, Gopalakrishnan S, Ding J, Li Y, Grimm S, Zollner S. 2010. Extending rare-variant testing strategies: analysis of noncoding sequence and imputed genotypes. Am J Hum Genet 87: 604-617.