Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles
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Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
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Many human studies have generated eQTL maps in tissues including brain, liver, skin, immune cells, and lymphoblastoid cell lines.
“Since then, numerous human studies have generated eQTLs maps in multiple tissues such as brain, liver, skin, immune cells, and lymphoblastoid cell lines (Ding et al., 2010; Fairfax et al., 2012; Myers et al., 2007; Pickrell et al., 2010; Schadt et al., 2008; Veyrieras et al., 2008; W. Zhang et al., 2008).”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Fairfax et al., 2012
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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 · see citing works
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J., Fry, B., Maller, J., & Daly, M. (2005) · Bioinform. · doi:10.1093/bioinformatics/bth457 · Cited by 15,086 · see citing works
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
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 · see citing works
Self-citationA map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
The ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223 · see citing works
Howie, B. N., Donnelly, P., & Marchini, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000529 · Cited by 3,928 · see citing works
LocusZoom: regional visualization of genome-wide association scan results
Pruim, R. J., Welch, R. P., Sanna, S., Teslovich, T. M., Chines, P. S., Gliedt, T. P., Boehnke, M., Abecasis, G. R., & Willer, C. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq419 · Cited by 2,707 · see citing works
A diverse range of gene products are effectors of the type I interferon antiviral response
Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, M. Y., Jones, C. T., Bieniasz, P. D., & Rice, C. M. (2011) · Nature · doi:10.1038/nature09907 · Cited by 2,439 · see citing works
Wellcome Trust Case Control Consortium, Zeggini, E., Scott, L. J., Saxena, R., Voight, B. F., Marchini, J. L., Hu, T., de Bakker, P. I., Abecasis, G. R., Almgren, P., et al. (2008) · Nature Genetics · doi:10.1038/ng.120 · Cited by 1,864 · see citing works
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 · see citing works
Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways
Nair, R. P., Duffin, K. C., Helms, C. A., Ding, J., Stuart, P. E., Goldgar, D. E., Gudjonsson, J. E., Li, Y., Tejasvi, T., Feng, B., et al. (2009) · Nature Genetics · doi:10.1038/ng.311 · Cited by 1,414 · see citing works
A new member of the immunoglobulin superfamily—CTLA-4
Brunet, J., Denizot, F., Luciani, M., Roux-Rouquié, M., Suzan, M., Mattéi, M., & Golstein, P. (1987) · Nature · doi:10.1038/328267a0 · Cited by 1,307 · see citing works
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296 · see citing works
A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
Fellay, J., Shianna, K. V., Ge, D., Colombo, S. F., Ledergerber, B., Weale, M., Zhang, K., Gumbs, C. E., Castagna, A., Cossarizza, A., et al. (2007) · Science · doi:10.1126/science.1143767 · Cited by 1,231 · see citing works
The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Study, T. I. H. C. (2010) · Science · doi:10.1126/science.1195271 · Cited by 1,162 · see citing works
Population genomics of human gene expression
Stranger, B. E., Nica, A. C., Forrest, M. S., Dimas, A. S., Bird, C., Beazley, C., Ingle, C., Dunning, M., Flicek, P., Koller, D., et al. (2007) · Nature Genetics · doi:10.1038/ng2142 · Cited by 1,132 · see citing works
Strange, A., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Pirinen, M., Rautanen, A., Su, Z., Donnelly, P., Capon, F., et al. (2010) · Nature Genetics · doi:10.1038/ng.694 · Cited by 1,042 · see citing works
Self-citationFilamins as integrators of cell mechanics and signalling
Stossel, T. P., Condeelis, J. S., Cooley, L., Hartwig, J. H., Noegel, A. A., Schleicher, M., & Shapiro, S. S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052082 · Cited by 1,021 · see citing works
A genome-wide association study of global gene expression
Dixon, A. L., Liang, L., Moffatt, M. F., Chen, W., Heath, S. C., Wong, K., Taylor, J. C., Burnett, E. C., Gut, I. G., Farrall, M., et al. (2007) · Nature Genetics · doi:10.1038/ng2109 · Cited by 946 · see citing works
Mapping the Genetic Architecture of Gene Expression in Human Liver
Schadt, E. E., Molony, C. M., Chudin, E., Hao, K., Yang, X., Lum, P. Y., Kasarskis, A., Zhang, B., Wang, S. S.-M., Suver, C., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060107 · Cited by 909 · see citing works
Evans, D. M., Spencer, C. C. A., Pointon, J. J., Su, Z., Harvey, D., Kochan, G. T., Oppermann, U. C. T., Dilthey, A., Pirinen, M., Stone, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.873 · Cited by 895 · see citing works
Self-citationThe Role of the Transcription Factor CREB in Immune Function
Wen, A. Y., Sakamoto, K. M., & Miller, L. S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001829 · Cited by 865 · see citing works
Mapping complex disease traits with global gene expression
Cookson, W., Liang, L., Abecasis, G., Moffatt, M., & Lathrop, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2537 · Cited by 849 · see citing works
The HLA genomic loci map: expression, interaction, diversity and disease
Shiina, T., Hosomichi, K., Inoko, H., & Kulski, J. K. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2008.5 · Cited by 788 · see citing works
Common Regulatory Variation Impacts Gene Expression in a Cell Type–Dependent Manner
Dimas, A. S., Deutsch, S., Stranger, B. E., Montgomery, S. B., Borel, C., Attar, H., Ingle, C., Beazley, C., Arcelus, M. G., Sekowska, M., et al. (2009) · Science · doi:10.1126/science.1174148 · Cited by 746 · see citing works
A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci
Liu, Y., Helms, C. A., Liao, W. J., Zaba, L. C., Duan, S., Gardner, J. M., Wise, C. A., Miner, A. G., Malloy, M. J., Pullinger, C. R., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000041 · Cited by 660 · see citing works
Barrett, J., Lee, J. C., Lees, C., Prescott, N., Anderson, C., Phillips, A., Wesley, E., Parnell, K. S., Zhang, H., Drummond, H., et al. (2009) · Nature Genetics · doi:10.1038/ng.483 · Cited by 602 · see citing works
Self-citationMapping 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. P., & Burdick, J. T. (2005) · Nature · doi:10.1038/nature04244 · Cited by 588 · see citing works
Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility
Zeller, T., Wild, P. S., Szymczak, S., Rotival, M., Schillert, A., Castagné, R., Maouche, S., Germain, M., Lackner, K. J., Rossmann, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010693 · Cited by 584 · see citing works
Nica, A. C., Montgomery, S. B., Dimas, A. S., Stranger, B. E., Beazley, C., Barroso, I., & Dermitzakis, E. T. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000895 · Cited by 423 · see citing works
The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study
Nica, A. C., Parts, L., Glass, D., Nisbet, J. P., Barrett, A., Sekowska, M., Travers, M. E., Potter, S., Grundberg, E., Small, K. S., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002003 · Cited by 395 · see citing works
Nonsyndromic hearing impairment is associated with a mutation in DFNA5
Laer, L. V., Huizing, E. H., Verstreken, M., Zuijlen, D. A. V., Wauters, J. G., Bossuyt, P., de Heyning, P. V., McGuirt, W. T., Smith, R. J., Willems, P. J., et al. (1998) · Nature Genetics · doi:10.1038/2503 · Cited by 390 · see citing works
FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling
Ohta, Y., Hartwig, J. H., & Stossel, T. P. (2006) · Nature Cell Biology · doi:10.1038/ncb1437 · Cited by 390 · see citing works
Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells
Gray, M., Miles, K., Salter, D. M., Gray, D., & Savill, J. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0700326104 · Cited by 340 · see citing works
Fehrmann, R. S. N., Jansen, R. C., Veldink, J. H., Westra, H.-J., Arends, D., Bonder, M. J., Fu, J., Deelen, P., Groen, H. J. M., Smolonska, A., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002197 · Cited by 330 · see citing works
Small, K. S., Grundberg, E., Soranzo, N., Ahmadi, K. R., Spector, T. D., Shin, S., Deloukas, P., Hedman, Å. K., Lindgren, C. M., McCarthy, M. I., et al. (2011) · Nature Genetics · doi:10.1038/ng.833 · Cited by 320 · see citing works
HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C
Thomas, R., Apps, R., Qi, Y., et al. (2009) · Nature Genetics · doi:10.1038/ng.486 · Cited by 283 · see citing works
Limou, S., Clerc, S. L., Coulonges, C., Carpentier, W., Dina, C., Delaneau, O., Labib, T., Taing, L., Sladek, R., Deveau, C., et al. (2009) · Journal of Infectious Diseases · doi:10.1086/596067 · Cited by 270 · see citing works
Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases
International MHC and Autoimmunity Genetics Network (IMAGEN)*, Rioux, J. D., Goyette, P., Vyse, T. J., Hammarström, L. L. G., Fernando, M. M. A., Green, T. J., Jager, P. L. D., Foisy, S., Wang, J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909307106 · Cited by 256 · see citing works
Self-citationAndrés, A. M., Dennis, M. Y., Kretzschmar, W. W., Cannons, J. L., Lee-Lin, S.-Q., Hurlé, B., Program, N. C. S., Schwartzberg, P. L., Williamson, S., Bustamante, C. D., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001157 · Cited by 242 · see citing works
Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer
Akino, K., Toyota, M., Suzuki, H., Imai, T., Maruyama, R., Kusano, M., Nishikawa, N., Watanabe, Y., Sasaki, Y., Abe, T., et al. (2006) · Cancer Science · doi:10.1111/j.1349-7006.2006.00351.x · Cited by 238 · see citing works
Tedder, T. F., & Isaacs, C. M. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.2.712 · Cited by 196 · see citing works
Landers, J. E., Melki, J., Meininger, V., Glass, J. D., van den Berg, L. H., van Es, M. A., Sapp, P. C., van Vught, P. W. J., McKenna-Yasek, D. M., Blauw, H. M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812937106 · Cited by 183 · see citing works
A Statistical Method for Predicting Classical HLA Alleles from SNP Data
Leslie, S., Donnelly, P., & McVean, G. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.001 · Cited by 173 · see citing works
Self-citationHLA*IMP—an integrated framework for imputing classical HLA alleles from SNP genotypes
Dilthey, A., Moutsianas, L., Leslie, S., & McVean, G. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr061 · Cited by 166 · see citing works
Self-citationGeographical genomics of human leukocyte gene expression variation in southern Morocco
Idaghdour, Y., Czika, W., Shianna, K. V., Lee, S. H., Visscher, P. M., Martin, H. C., Miclaus, K., Jadallah, S. J., Goldstein, D. B., Wolfinger, R. D., et al. (2010) · Nature Genetics · doi:10.1038/ng.495 · Cited by 151 · see citing works
Hakonarson, H. H., Qu, H., Bradfield, J. P., Marchand, L., Kim, C., Glessner, J., Grabs, R., Casalunovo, T., Taback, S. P., Frackelton, E. C., et al. (2008) · Diabetes · doi:10.2337/db07-1305 · Cited by 150 · see citing works
Elstak, E., Neeft, M., Nehme, N. T., Voortman, J., Cheung, M., Goodarzifard, M., Gerritsen, H. C., Henegouwen, P. M. P. V. B. E., Callebaut, I., Basile, G. D. S., et al. (2011) · Blood · doi:10.1182/blood-2011-02-339523 · Cited by 139 · see citing works
Ho, P., Barton, A. C., Worthington, J., et al. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.071399 · Cited by 122 · see citing works
Plagnol, V., Smyth, D. J., Todd, J. A., & Clayton, D. G. (2009) · Biostatistics · doi:10.1093/biostatistics/kxn039 · Cited by 113 · see citing works
p53-mediated apoptosis requires inositol hexakisphosphate kinase-2
Koldobskiy, M. A., Chakraborty, A., Werner, J. K., Snowman, A. M., Juluri, K. R., Vandiver, M. S., Kim, S., Heletz, S., & Snyder, S. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015671107 · Cited by 110 · see citing works
Lyons, P., Koukoulaki, M., Hatton, A., Doggett, K., Woffendin, H. B., Chaudhry, A., & Smith, K. G. C. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-64 · Cited by 109 · see citing works
CARD9 Signaling in the Innate Immune Response
Ruland, J. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.024 · Cited by 105 · see citing works
Xu, H., Manivannan, A., Crane, I. J., Dawson, R., & Liversidge, J. (2008) · Blood · doi:10.1182/blood-2007-06-098327 · Cited by 94 · see citing works
Expression Quantitative Trait Loci Are Highly Sensitive to Cellular Differentiation State
Gerrits, A., Li, Y., Tesson, B. M., Bystrykh, L. V., Weersing, E., Ausema, A., Dontje, B., Wang, X., Breitling, R., Jansen, R. C., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000692 · Cited by 91 · see citing works
Fischer, U., Heckel, D., Michel, A., et al. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1817 · Cited by 87 · see citing works
Vandiedonck, C., Taylor, M. S., Lockstone, H. E., Plant, K., Taylor, J. M., Durrant, C., Broxholme, J., Fairfax, B. P., & Knight, J. C. (2011) · Genome Research · doi:10.1101/gr.116681.110 · Cited by 68 · see citing works
Self-citationHagen, F. S., Grant, F. J., Kuijper, J. L., et al. (1991) · Biochemistry · doi:10.1021/bi00098a020 · Cited by 67 · see citing works
Lawson, B. R., Baccalà, R., Song, J. J., Croft, M., Kono, D. H., & Theofilopoulos, A. N. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031685 · Cited by 65 · see citing works
Tissue Effect on Genetic Control of Transcript Isoform Variation
Kwan, T., Grundberg, E., Koka, V., Ge, B., Lam, K. C. L., Dias, C., Kindmark, A., Mallmin, H., Ljunggren, Ö., Rivadeneira, F., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000608 · Cited by 57 · see citing works
Def‐2, ‐3, ‐6 and ‐8, novel mouse genes differentially expressed in the haemopoietic system
Hotfilder, M., Baxendale, S., Cross, M. A., & Sablitzky, F. (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01551.x · Cited by 55 · see citing works
Tomaru, T., Satoh, T., Yoshino, S., Ishizuka, T., Hashimoto, K., Monden, T., Yamada, M., & Mori, M. (2005) · Endocrinology · doi:10.1210/en.2005-0450 · Cited by 48 · see citing works
Lavelin, I., & Geiger, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411990200 · Cited by 42 · see citing works
Knowles, R. W., Flomenberg, N., Horibe, K., et al. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.8.2618 · Cited by 36 · see citing works
Kim, K., Sung, Y.-K., Kang, C., et al. (2009) · Genes and Immunity · doi:10.1038/gene.2009.5 · Cited by 28 · see citing works
Neznanov, N. S., Neznanova, L., Angres, B., et al. (2005) · DNA and Cell Biology · doi:10.1089/dna.2005.24.777 · Cited by 23 · see citing works
Glycosylation regulates NK cell-mediated effector function through PI3K pathway
Benson, V., Grobárová, V., Richter, J., & Fišerová, A. (2010) · International Immunology · doi:10.1093/intimm/dxp123 · Cited by 21 · see citing works
Identification of the MT3 molecule from HLA-DR4, 7, and w9 homozygous cell lines.
Mukai, R., Suzuki, M., Yabe, T., et al. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.6.3211 · Cited by 14 · see citing works
Small, K. S., Hedman, Å. K., Grundberg, E., Nica, A. C., Þorleifsson, G., Kong, A., Thorsteindottir, U., Shin, S., Richards, H. B., Soranzo, N., et al. (2011) · Surrey Research Insight Open Access (The University of Surrey) · doi:10.1038/ng1011-1040c · Cited by 7 · see citing works
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Visscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
Systematic identification of trans eQTLs as putative drivers of known disease associations
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) · Nature Genetics · doi:10.1038/ng.2756 · Cited by 1,658 · see citing works
Self-citationWightman, D. P., Jansen, I. E., Savage, J. E., Shadrin, A. A., Bahrami, S., Holland, D., Rongve, A., Børte, S., Winsvold, B. S., Drange, O. K., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00921-z · Cited by 1,011 · see citing works
The role of regulatory variation in complex traits and disease
Albert, F. W., & Kruglyak, L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3891 · Cited by 1,047 · see citing works
Javierre, B. M., Burren, O. S., Wilder, S. P., Kreuzhuber, R., Hill, S. M., Sewitz, S., Cairns, J., Wingett, S. W., Várnai, C., Thiecke, M. J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.037 · Cited by 1,046 · see citing works
Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression
Fairfax, B. P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C., et al. (2014) · Science · doi:10.1126/science.1246949 · Cited by 764 · see citing works
Self-citationThe International IBD Genetics Consortium (IIBDGC), Ellinghaus, D., International Genetics of Ankylosing Spondylitis Consortium (IGAS), International PSC Study Group (IPSCSG), Genetic Analysis of Psoriasis Consortium (GAPC), Psoriasis Association Genetics Extension (PAGE), Jostins, L., Spain, S. L., Cortes, A., Bethune, J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3528 · Cited by 751 · see citing works
Validating therapeutic targets through human genetics
Plenge, R. M., Scolnick, E. M., & Altshuler, D. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4051 · Cited by 712 · see citing works
Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease
Yazar, S., Alquicira-Hernandez, J., Wing, K., Senabouth, A., Gordon, M. G., Andersen, S., Lu, Q., Rowson, A., Taylor, T. R. P., Clarke, L., et al. (2022) · Science · doi:10.1126/science.abf3041 · Cited by 682 · see citing works
Genetic variability in the regulation of gene expression in ten regions of the human brain
UK Brain Expression Consortium, Ramasamy, A., North American Brain Expression Consortium, Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T., Coin, L., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3801 · Cited by 644 · see citing works
Chromatin marks identify critical cell types for fine mapping complex trait variants
Trynka, G., Sandor, C., Han, B., Xu, H., Stranger, B. E., Liu, X. S., & Raychaudhuri, S. (2013) · Nature Genetics · doi:10.1038/ng.2504 · Cited by 580 · see citing works
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. (2014) · Genome Research · doi:10.1101/gr.155192.113 · Cited by 547 · see citing works
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
Study, A. O. C., Perry, J. R. B., The GENICA Network, kConFab, Study, T. L. C., The InterAct Consortium, Early Growth Genetics (EGG) Consortium, Day, F., Elks, C. E., Sulem, P., et al. (2014) · Nature · doi:10.1038/nature13545 · Cited by 604 · see citing works
Self-citationShared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
23andMe Research Team, Ferreira, M. A., collaborators, A., BIOS consortium, Study, L. C., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., et al. (2017) · Nature Genetics · doi:10.1038/ng.3985 · Cited by 550 · see citing works
Schwartzentruber, J., Cooper, S., Liu, J. Z., Barrio-Hernandez, I., Bello, E., Kumasaka, N., Young, A. M. H., Franklin, R. J. M., Johnson, T., Estrada, K., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00776-w · Cited by 532 · see citing works
Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
Raj, T., Rothamel, K., Mostafavi, S., Ye, C., Lee, M. N., Replogle, J. M., Feng, T., Lee, M., Asinovski, N., Frohlich, I., et al. (2014) · Science · doi:10.1126/science.1249547 · Cited by 506 · see citing works
Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs
Study, L. C., van der Wijst, M. G. P., BIOS Consortium, Brugge, H., de Vries, D. H., Deelen, P., Swertz, M. A., & Franke, L. (2018) · Nature Genetics · doi:10.1038/s41588-018-0089-9 · Cited by 399 · see citing works
Computational principles and challenges in single-cell data integration
Argelaguet, R., Cuomo, A. S. E., Stegle, O., & Marioni, J. C. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00895-7 · Cited by 472 · see citing works
Sun, Y. V., & Hu, Y.-J. (2016) · Advances in Genetics · doi:10.1016/bs.adgen.2015.11.004 · Cited by 459 · see citing works
Qi, T., Wu, Y., Zeng, J., Zhang, F., Xue, A., Jiang, L., Zhu, Z., Kemper, K., Yengo, L., Zheng, Z., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04558-1 · Cited by 427 · see citing works
The UK-PSC Consortium, Ji, S.-G., The International IBD Genetics Consortium, The International PSC Study Group, Juran, B. D., Mucha, S., Folseraas, T., Jostins, L., Melum, E., Kumasaka, N., et al. (2017) · Nature Genetics · doi:10.1038/ng.3745 · Cited by 357 · see citing works
Heritability and genomics of gene expression in peripheral blood
Wright, F. A., Sullivan, P. F., Brooks, A. I., Zou, F., Sun, W., Xia, K., Madar, V., Jansen, R., Chung, W., Zhou, Y.-H., et al. (2014) · Nature Genetics · doi:10.1038/ng.2951 · Cited by 362 · see citing works
Robertson, C. C., Inshaw, J. R. J., Onengut-Gumuscu, S., Chen, W.-M., Santa Cruz, D. F., Yang, H., Cutler, A. J., Crouch, D. J. M., Farber, E., Bridges, S. L., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00880-5 · Cited by 302 · see citing works
Where Are the Disease-Associated eQTLs?
Umans, B. D., Battle, A., & Gilad, Y. (2021) · Trends in Genetics · doi:10.1016/j.tig.2020.08.009 · Cited by 296 · see citing works
A Role for Noncoding Variation in Schizophrenia
Roussos, P., Mitchell, A. C., Voloudakis, G., Fullard, J. F., Pothula, V. M., Tsang, J., Stahl, E. A., Georgakopoulos, A., Ruderfer, D. M., Charney, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.015 · Cited by 251 · see citing works
Resolving <i>TYK2</i> locus genotype-to-phenotype differences in autoimmunity
Dendrou, C. A., Cortes, A., Shipman, L., Evans, H. G., Attfield, K. E., Jostins, L., Barber, T., Kaur, G., Kuttikkatte, S. B., Leach, O. A., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag1974 · Cited by 264 · see citing works
Australian Asthma Genetics Consortium (AAGC), Bønnelykke, K., the EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Matheson, M. C., Pers, T. H., Granell, R., Strachan, D. P., Alves, A. C., Linneberg, A., Curtin, J. A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2694 · Cited by 244 · see citing works
Self-citationGene expression drives local adaptation in humans
Fraser, H. B. (2013) · Genome Research · doi:10.1101/gr.152710.112 · Cited by 247 · see citing works
Ferreira, M. A. R., Matheson, M. C., Tang, C. S., Granell, R., Ang, W., Hui, J., Kiefer, A. K., Duffy, D. L., Baltic, S., Danoy, P., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.10.030 · Cited by 216 · see citing works
Population Variation and Genetic Control of Modular Chromatin Architecture in Humans
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. (2015) · Cell · doi:10.1016/j.cell.2015.08.001 · Cited by 214 · see citing works
Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments
Gittelman, R. M., Schraiber, J. G., Vernot, B., Mikacenic, C., Wurfel, M. M., & Akey, J. M. (2016) · Current Biology · doi:10.1016/j.cub.2016.10.041 · Cited by 181 · see citing works
Small, K. S., Todorčević, M., Civelek, M., El-Sayed Moustafa, J. S., Wang, X., Simon, M. M., Fernandez-Tajes, J., Mahajan, A., Horikoshi, M., Hugill, A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0088-x · Cited by 168 · see citing works
Insights into TREM2 biology by network analysis of human brain gene expression data
Forabosco, P., Ramasamy, A., Trabzuni, D., Walker, R., Smith, C., Bras, J., Levine, A. P., Hardy, J., Pocock, J. M., Guerreiro, R., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.001 · Cited by 180 · see citing works
Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
Shi, J., Marconett, C. N., Duan, J., Hyland, P. L., Li, P., Wang, Z., Wheeler, W., Zhou, B., Campan, M., Lee, D. S., et al. (2014) · Nature Communications · doi:10.1038/ncomms4365 · Cited by 137 · see citing works
Single-cell genomics meets human genetics
Cuomo, A. S. E., Nathan, A., Raychaudhuri, S., MacArthur, D. G., & Powell, J. E. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00599-5 · Cited by 124 · see citing works
Statistical Testing of Shared Genetic Control for Potentially Related Traits
Wallace, C. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21765 · Cited by 115 · see citing works
Prediction of Causal Candidate Genes in Coronary Artery Disease Loci
Brænne, I., Civelek, M., Vilne, B., Di Narzo, A., Johnson, A. D., Zhao, Y., Reiz, B., Codoni, V., Webb, T. R., Foroughi Asl, H., et al. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.306108 · Cited by 109 · see citing works
Janelsins, B. M., Lu, M., & Datta, S. K. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311987111 · Cited by 56 · see citing works
Hu, X., Kim, H., Raj, T., Brennan, P. J., Trynka, G., Teslovich, N., Slowikowski, K., Chen, W.-M., Onengut, S., Baecher-Allan, C., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004404 · Cited by 52 · see citing works
Hause, R. J., Stark, A. L., Antao, N. N., Gorsic, L. K., Chung, S. H., Brown, C. D., Wong, S. S., Gill, D. F., Myers, J. L., To, L. A., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.07.005 · Cited by 43 · see citing works
Genetics of endometriosis: state of the art on genetic risk factors for endometriosis
Fung, J. N., & Montgomery, G. W. (2018) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2018.01.012 · Cited by 41 · see citing works
Mapping the Genetic Architecture of Gene Regulation in Whole Blood
Schramm, K., Marzi, C., Schurmann, C., Carstensen, M., Reinmaa, E., Biffar, R., Eckstein, G., Gieger, C., Grabe, H.-J., Homuth, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093844 · Cited by 33 · see citing works
Wang, T., Peng, Q., Liu, B., Liu, Y., & Wang, Y. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00418 · Cited by 27 · see citing works
Expression quantitative trait locus studies in the era of single-cell omics
Luo, J., Wu, X., Cheng, Y., Chen, G., Wang, J., & Song, X. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1182579 · Cited by 11 · see citing works
Demultiplexing of single-cell RNA-sequencing data using interindividual variation in gene expression
Nassiri, I., Kwok, A. J., Bhandari, A., Bull, K. R., Garner, L. C., Klenerman, P., Webber, C., Parkkinen, L., Lee, A. W., Wu, Y., et al. (2024) · Bioinformatics Advances · doi:10.1093/bioadv/vbae085 · Cited by 8 · see citing works
Self-citation
- Authors
- Fairfax, B. P., Makino, S., Radhakrishnan, J., Plant, K., Leslie, S., Dilthey, A., Ellis, P., Langford, C., Vannberg, F. O., & Knight, J. C.
- Affiliations
- Centre for Human Genetics (GB)
- University of Oxford (GB)
- University of Cambridge (GB)
- Georgia Institute of Technology (US)
- Corresponding author
- Fairfax, Benjamin P
- Knight, Julian C
- ORCID
- Venue
- Nature Genetics
- Published
- 2012-03-25
- Volume
- 44
- Issue
- 5
- Pages
- 502-510
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3437404
- OpenAlex
- W2035451872
- Cited by
- 486
- References
- 70
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 26 · 2023: 24 · 2022: 25 · 2021: 24 · 2020: 30 · 2019: 34 · 2018: 41 · 2017: 34 · 2016: 55 · 2015: 47 · 2014: 55 · 2013: 47 · 2012: 12
- FWCI
- 30.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Wellcome Trust (075491, 088891, 074318, 075491/Z/04,, 090532)
- National Institute for Health and Care Research (ACF-2008-13-017)
- European Commission
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- expression quantitative trait loci, cell type-specific gene regulation, primary monocytes, B cells, HLA alleles, autoimmune disease susceptibility, lysozyme, KLF4, p21, PPARγ signaling, cell cycle regulation, ARHGAP24
- MeSH terms
- Kruppel-Like Factor 4, Alleles, Autoimmune Diseases, B-Lymphocytes, Gene Expression Regulation, Genetic Markers, HLA Antigens, Humans, Monocytes, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Quantitative Trait Loci, PPAR gamma, Kruppel-Like Transcription Factors, Genome-Wide Association Study
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