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Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits
Open accessAbstract
Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes.
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Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,684
Listening to silence and understanding nonsense: exonic mutations that affect splicing
Cartegni, L., Chew, S. L., & Krainer, A. R. (2002) · Nature Reviews Genetics · doi:10.1038/nrg775 · Cited by 2,209
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study
(2007) · New England Journal of Medicine · doi:10.1056/nejmoa073493 · Cited by 1,746
Large recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745
Self-citationAssociation between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa075974 · Cited by 1,666
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
Moffatt, M. F., Kabesch, M., Liang, L., Dixon, A. L., Strachan, D., Heath, S., Depner, M., von Berg, A., Bufe, A., Rietschel, E., et al. (2007) · Nature · doi:10.1038/nature06014 · Cited by 1,604
Newly identified loci that influence lipid concentrations and risk of coronary artery disease
Willer, C. J., Sanna, S., Jackson, A. U., Scuteri, A., Bonnycastle, L. L., Clarke, R., Heath, S. C., Timpson, N. J., Najjar, S. S., Stringham, H. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.76 · Cited by 1,585
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Finland, G. O. T. 1. D. I., Todd, J. A., the Wellcome Trust Case Control Consortium, Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., et al. (2007) · Nature Genetics · doi:10.1038/ng2068 · Cited by 1,456
A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes
Bottini, N., Musumeci, L., Alonso, A., Rahmouni, S., Nika, K., Rostamkhani, M., MacMurray, J., Meloni, G. F., Lucarelli, P., Pellecchia, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1323 · Cited by 1,424
Kathiresan, S., Melander, O., Guiducci, C., Surti, A., Burtt, N. P., Rieder, M. J., Cooper, G. M., Roos, C., Voight, B. F., Havulinna, A. S., et al. (2008) · Nature Genetics · doi:10.1038/ng.75 · Cited by 1,386
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Wellcome Trust Case Control Consortium, & The Australo-Anglo-American Spondylitis Consortium (TASC) (2007) · Nature Genetics · doi:10.1038/ng.2007.17 · Cited by 1,374
The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley, J. B., Alarcón-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., Tsao, B. P., Vyse, T. J., & Langefeld, C. D. (2008) · Nature Genetics · doi:10.1038/ng.81 · Cited by 1,309
Yanai, I., Benjamin, H., Shmoish, M., Chalifa-Caspi, V., Shklar, M., Ophir, R., Bar-Even, A., Horn-Saban, S., Safran, M., Domany, E., et al. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti042 · Cited by 1,300
A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
Fellay, J., Shianna, K. V., Ge, D., Colombo, S., Ledergerber, B., Weale, M., Zhang, K., Gumbs, C., Castagna, A., Cossarizza, A., et al. (2007) · Science · doi:10.1126/science.1143767 · Cited by 1,235
Self-citationA genome-wide association study of global gene expression
Dixon, A. L., Liang, L., Moffatt, M. F., Chen, W., Heath, S., Wong, K. C. C., Taylor, J., Burnett, E., Gut, I., Farrall, M., et al. (2007) · Nature Genetics · doi:10.1038/ng2109 · Cited by 953
Mapping the Genetic Architecture of Gene Expression in Human Liver
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) · PLoS Biology · doi:10.1371/journal.pbio.0060107 · Cited by 921
Association of Systemic Lupus Erythematosus with C8orf13–BLK and ITGAM–ITGAX
Hom, G., Graham, R. R., Modrek, B., Taylor, K. E., Ortmann, W., Garnier, S., Lee, A. T., Chung, S. A., Ferreira, R. C., Pant, P. V. K., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0707865 · Cited by 914
van Heel, D. A., Franke, L., Hunt, K. A., Gwilliam, R., Zhernakova, A., Inouye, M., Wapenaar, M. C., Barnardo, M. C. N. M., Bethel, G., Holmes, G. K. T., et al. (2007) · Nature Genetics · doi:10.1038/ng2058 · Cited by 669
Association Between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000316305.61461.6f · Cited by 647
Mapping determinants of human gene expression by regional and genome-wide association
Cheung, V. G., Spielman, R. S., Ewens, K. G., Weber, T. M., Morley, M., & Burdick, J. T. (2005) · Nature · doi:10.1038/nature04244 · Cited by 588
Plenge, R. M., Padyukov, L., Remmers, E. F., Purcell, S., Lee, A. T., Karlson, E. W., Wolfe, F., Kastner, D. L., Alfredsson, L., Altshuler, D., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/498651 · Cited by 564
Libioulle, C., Louis, E., Hansoul, S., Sandor, C., Farnir, F., Franchimont, D., Vermeire, S., Dewit, O., de Vos, M., Dixon, A., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030058 · Cited by 560
Genome-Wide Associations of Gene Expression Variation in Humans
Stranger, B. E., Forrest, M. S., Clark, A. G., Minichiello, M. J., Deutsch, S., Lyle, R., Hunt, S., Kahl, B., Antonarakis, S. E., Tavaré, S., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010078 · Cited by 519
Common Sequence Variants in the LOXL1 Gene Confer Susceptibility to Exfoliation Glaucoma
Myers, J. S. (2008) · Yearbook of Ophthalmology · doi:10.1016/s0084-392x(08)79151-2 · Cited by 517
A survey of genetic human cortical gene expression
Myers, A. J., Gibbs, J. R., Webster, J. A., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., Leung, D., Bryden, L., Nath, P., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.16 · Cited by 479
Messenger RNA regulation: to translate or to degrade
Shyu, A., Wilkinson, M. F., & van Hoof, A. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601977 · Cited by 447
Genome-wide analysis of transcript isoform variation in humans
Kwan, T., Benovoy, D., Dias, C., Gurd, S., Provencher, C., Beaulieu, P., Hudson, T. J., Sladek, R., & Majewski, J. (2008) · Nature Genetics · doi:10.1038/ng.2007.57 · Cited by 305
Evaluation of Genetic Variation Contributing to Differences in Gene Expression between Populations
Zhang, W., Duan, S., Kistner, E. O., Bleibel, W. K., Huang, R. S., Clark, T. A., Chen, T. X., Schweitzer, A. C., Blume, J. E., Cox, N. J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.015 · Cited by 200
Identification of Common Genetic Variation That Modulates Alternative Splicing
Hull, J., Campino, S. G., Rowlands, K., Chan, M., Copley, R. R., Taylor, M. S., Rockett, K. A., Elvidge, G. P., Keating, B. J., Knight, J. C., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030099 · Cited by 168
Human Genetics: The Hidden Text of Genome-wide Associations
Gibson, G. C., & Goldstein, D. B. (2007) · Current Biology · doi:10.1016/j.cub.2007.08.044 · Cited by 19
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Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, E. T., & Goldstein, D. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2779 · Cited by 1,136
Self-citationCommon genetic variants on 5p14.1 associate with autism spectrum disorders
Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J. T., Abrahams, B. S., Salyakina, D., Imielinski, M., Bradfield, J. P., Sleiman, P. M. A., et al. (2009) · Nature · doi:10.1038/nature07999 · Cited by 989
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Study, L. C., Köttgen, A., CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium, Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2500 · Cited by 836
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
Rietveld, C. A., Medland, S. E., Derringer, J., Yang, J., Esko, T., Martin, N. W., Westra, H.-J., Shakhbazov, K., Abdellaoui, A., Agrawal, A., et al. (2013) · Science · doi:10.1126/science.1235488 · Cited by 827
Metadata
- Authors
- Heinzen, E. L., Ge, D., Cronin, K. D., Maia, J. M., Shianna, K. V., Gabriel, W. N., Welsh-Bohmer, K. A., Hulette, C. M., Denny, T. N., & Goldstein, D. B.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-12-23
- Volume
- 6
- Issue
- 12
- Pages
- e1000001
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2049231704
- Cited by
- 269
- References
- 34
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- gold
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