HaploReg v4: Systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease

Nucleic Acids Research

Volumn 44, Issue D1, 2016, Pages D877-D881

  Ward, Lucas D ^a,b,c   Kellis, Manolis ^a,b  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; ATTENTION DEFICIT DISORDER; BINDING SITE; CATALOGING DATABASE; CELL FUNCTION; CELLS BY BODY ANATOMY; CHROMATIN STRUCTURE; COMPUTER ANALYSIS; COMPUTER INTERFACE; COMPUTER PREDICTION; COMPUTER PROGRAM; DATA MINING; EPIGENETICS; GENE EXPRESSION; GENE SEQUENCE; GENE TARGETING; GENETIC ASSOCIATION; GENETIC DATABASE; GENETIC REGULATION; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HAPLOREG V4; HAPLOTYPE; HUMAN; PRIORITY JOURNAL; PROTEIN BINDING; QUANTITATIVE TRAIT LOCUS; REGULATOR GENE; REGULATORY MECHANISM; SINGLE NUCLEOTIDE POLYMORPHISM; WEB BROWSER; DISEASES; GENE; GENETICS; METABOLISM; REGULATORY SEQUENCE;

TRANSCRIPTION FACTOR;

ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; BINDING SITES; DATA MINING; DATABASES, GENETIC; DISEASE; EPIGENOMICS; GENE EXPRESSION; GENES; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HAPLOTYPES; HUMANS; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; REGULATORY SEQUENCES, NUCLEIC ACID; TRANSCRIPTION FACTORS;

EID: 84976873328     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkv1340     Document Type: Article

References (42)

1. Ward, L. D. and Kellis, M. (2012) Interpreting noncoding genetic variation in complex traits and human disease. Nat. Biotechnol., 30, 1095-1106.
2. Paul, D. S., Soranzo, N. and Beck, S. (2014) Functional interpretation of non-coding sequence variation: concepts and challenges. Bioessays, 36, 191-199.
3. Civelek, M. and Lusis, A. J. (2014) Systems genetics approaches to understand complex traits. Nat. Rev. Genet., 15, 34-48.
4. Ward, L. D. and Kellis, M. (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res., 40, D930-D934.
5. Verhoeven, V. J., Hysi, P. G., Wojciechowski, R., Fan, Q., Guggenheim, J. A., Hohn, R., MacGregor, S., Hewitt, A. W., Nag, A., Cheng, C. Y. et al. (2013) Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat. Genet., 45, 314-318.
6. Chung, C. C., Kanetsky, P. A., Wang, Z., Hildebrandt, M. A., Koster, R., Skotheim, R. I., Kratz, C. P., Turnbull, C., Cortessis, V. K., Bakken, A. C. et al. (2013) Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat. Genet., 45, 680-685.
7. Lee, M. N., Ye, C., Villani, A. C., Raj, T., Li, W., Eisenhaure, T. M., Imboywa, S. H., Chipendo, P. I., Ran, F. A., Slowikowski, K. et al. (2014) Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science, 343, 1246980.
8. Ruark, E., Seal, S., McDonald, H., Zhang, F., Elliot, A., Lau, K., Perdeaux, E., Rapley, E., Eeles, R., Peto, J. et al. (2013) Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14. Nat. Genet., 45, 686-689.
9. Franceschini, N., Fox, E., Zhang, Z., Edwards, T. L., Nalls, M. A., Sung, Y. J., Tayo, B. O., Sun, Y. V., Gottesman, O., Adeyemo, A. et al. (2013) Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. Am. J. Hum. Genet., 93, 545-554.
10. Westra, H. J., Peters, M. J., Esko, T., Yaghootkar, H., Schurmann, C., Kettunen, J., Christiansen, M. W., Fairfax, B. P., Schramm, K., Powell, J. E. et al. (2013) Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet., 45, 1238-1243.
11. Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J. et al. (2015) Integrative analysis of 111 reference human epigenomes. Nature, 518, 317-330.
12. Sherry, S. T., Ward, M.-H., Kholodov, M., Baker, J., Phan, L., Smigielski, E. M. and Sirotkin, K. (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res., 29, 308-311.
13. Quinlan, A. R. and Hall, I. M. (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics, 26, 841-842.
14. 1000 Genomes Project Consortium, Abecasis, G. R., Auton, A., Brooks, L. D., DePristo, M. A., Durbin, R. M., Handsaker, R. E., Kang, H. M., Marth, G. T. and McVean, G. A. (2012) An integrated map of genetic variation from 1, 092 human genomes. Nature, 491, 56-65.
15. Harrow, J., Denoeud, F., Frankish, A., Reymond, A., Chen, C. K., Chrast, J., Lagarde, J., Gilbert, J. G., Storey, R., Swarbreck, D. et al. (2006) GENCODE: producing a reference annotation for ENCODE. Genome Biol., 7(Suppl. 1), S4.1-S4.9.
16. Pruitt, K. D., Tatusova, T. and Maglott, D. R. (2007) NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res., 35, D61-D65.
17. Welter, D., MacArthur, J., Morales, J., Burdett, T., Hall, P., Junkins, H., Klemm, A., Flicek, P., Manolio, T., Hindorff, L. et al. (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res., 42, D1001-D1006.
18. Lindblad-Toh, K., Garber, M., Zuk, O., Lin, M. F., Parker, B. J., Washietl, S., Kheradpour, P., Ernst, J., Jordan, G., Mauceli, E. et al. (2011) A high-resolution map of human evolutionary constraint using 29 mammals. Nature, 478, 476-482.
19. Davydov, E. V., Goode, D. L., Sirota, M., Cooper, G. M., Sidow, A. and Batzoglou, S. (2010) Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput. Biol., 6, e1001025.
20. Encode Project Consortium. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57-74.
21. Ernst, J. and Kellis, M. (2015) Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues. Nat. Biotechnol., 33, 364-376.
22. GTEx Consortium. (2015) Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science, 348, 648-660.
23. Lappalainen, T., Sammeth, M., Friedlander, M. R., T Hoen, P. A., Monlong, J., Rivas, M. A., Gonzalez-Porta, M., Kurbatova, N., Griebel, T., Ferreira, P. G. et al. (2013) Transcriptome and genome sequencing uncovers functional variation in humans. Nature, 501, 506-511.
24. Montgomery, S. B., Sammeth, M., Gutierrez-Arcelus, M., Lach, R. P., Ingle, C., Nisbett, J., Guigo, R. and Dermitzakis, E. T. (2010) Transcriptome genetics using second generation sequencing in a Caucasian population. Nature, 464, 773-777.
25. Schadt, E. E., Molony, C., Chudin, E., Hao, K., Yang, X., Lum, P. Y., Kasarskis, A., Zhang, B., Wang, S., Suver, C. et al. (2008) Mapping the genetic architecture of gene expression in human liver. PLoS Biol., 6, e107.
26. Gibbs, J. R., Van Der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S. L., Arepalli, S., Dillman, A., Rafferty, I. P., Troncoso, J. et al. (2010) Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet., 6, e1000952.
27. Stranger, B. E., Nica, A. C., Forrest, M. S., Dimas, A., Bird, C. P., Beazley, C., Ingle, C. E., Dunning, M., Flicek, P., Koller, D. et al. (2007) Population genomics of human gene expression. Nat. Genet., 39, 1217-1224.
28. Li, Q., Stram, A., Chen, C., Kar, S., Gayther, S., Pharoah, P., Haiman, C., Stranger, B., Kraft, P. and Freedman, M. L. (2014) Expression QTL-based analyses reveal candidate causal genes and loci across five tumor types. Hum. Mol. Genet., 23, 5294-5302.
29. Zou, F., Chai, H. S., Younkin, C. S., Allen, M., Crook, J., Pankratz, V. S., Carrasquillo, M. M., Rowley, C. N., Nair, A. A., Middha, S. et al. (2012) Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants. PLoS Genet., 8, e1002707.
30. Koopmann, T. T., Adriaens, M. E., Moerland, P. D., Marsman, R. F., Westerveld, M. L., Lal, S., Zhang, T., Simmons, C. Q., Baczko, I., Dos Remedios, C. et al. (2014) Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart. PLoS One, 9, e97380.
31. Ramasamy, A., Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T. and U. K. Brain Expression Consortium, North American Brain Expression Consortium U. K. Brain Expression Consortium, North American Brain Expression Consortium and Coin, L. et al. (2014) Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat. Neurosci., 17, 1418-1428.
32. Fairfax, B. P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C. et al. (2014) Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science, 343, 1246949.
33. Grundberg, E., Adoue, V., Kwan, T., Ge, B., Duan, Q. L., Lam, K. C., Koka, V., Kindmark, A., Weiss, S. T., Tantisira, K. et al. (2011) Global analysis of the impact of environmental perturbation on cis-regulation of gene expression. PLoS Genet., 7, e1001279.
34. Hao, K., Bosse, Y., Nickle, D. C., Pare, P. D., Postma, D. S., Laviolette, M., Sandford, A., Hackett, T. L., Daley, D., Hogg, J. C. et al. (2012) Lung eQTLs to help reveal the molecular underpinnings of asthma. PLoS Genet., 8, e1003029.
35. Eicher, J. D., Landowski, C., Stackhouse, B., Sloan, A., Chen, W., Jensen, N., Lien, J. P., Leslie, R. and Johnson, A. D. (2015) GRASP v2.0: an update on the Genome-Wide Repository of Associations between SNPs and phenotypes. Nucleic Acids Res., 43, D799-D804.
36. Leslie, R., O'Donnell, C. J. and Johnson, A. D. (2014) GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database. Bioinformatics, 30, i185-i194.
37. Kheradpour, P. and Kellis, M. (2014) Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments. Nucleic Acids Res., 42, 2976-2987.
38. Lesch, K. P., Timmesfeld, N., Renner, T. J., Halperin, R., Roser, C., Nguyen, T. T., Craig, D. W., Romanos, J., Heine, M., Meyer, J. et al. (2008) Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J. Neural Transm., 115, 1573-1585.
39. Fehrmann, R. S., Jansen, R. C., Veldink, J. H., Westra, H. J., Arends, D., Bonder, M. J., Fu, J., Deelen, P., Groen, H. J., Smolonska, A. et al. (2011) Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet., 7, e1002197.
40. Suhre, K., Shin, S. Y., Petersen, A. K., Mohney, R. P., Meredith, D., Wagele, B., Altmaier, E., CardioGram, Deloukas, P., Erdmann, J. et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature, 477, 54-60.
41. Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Martino, A., Milham, M. P. and Castellanos, F. X. (2012) Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am. J. Psychiatry, 169, 1038-1055.
42. Eppig, J. T., Blake, J. A., Bult, C. J., Kadin, J. A., Richardson, J. E. and Mouse Genome Database, G. (2015) The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease. Nucleic Acids Res., 43, D726-D736.