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- Momozawa, YUnit of Animal Genomics, WELBIO, GIGA-R, Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Science, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan (author)
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- Article/chapterEnglish2018
Publisher, publication year, extent ...
- 2018-06-21
- Springer Science and Business Media LLC,2018
Numbers
- LIBRIS-ID:oai:prod.swepub.kib.ki.se:138576159
- http://kipublications.ki.se/Default.aspx?queryparsed=id:138576159URI
- https://doi.org/10.1038/s41467-018-04365-8DOI
- https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-68044URI
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- Language:English
- Summary in:English
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- Funding Agencies:WELBIO (CAUSIBD) BELSPO (BeMGI) Horizon 2020 (SYSCID) Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) 2.5020.11 Japan Agency for Medical Research and Development Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government Russian Ministry of Science and Education under 5-100 Excellence Programme VIDI grant from the Netherlands Organisation for Scientific Research (NWO) 016.136.308 Netherlands Federation of University Medical Centres Dutch Government
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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- Dmitrieva, J (author)
- Theatre, E (author)
- Deffontaine, V (author)
- Rahmouni, S (author)
- Charloteaux, B (author)
- Crins, F (author)
- Docampo, E (author)
- Elansary, M (author)
- Gori, AS (author)
- Lecut, C (author)
- Mariman, R (author)
- Mni, MKarolinska Institutet (author)
- Oury, C (author)
- Altukhov, I (author)
- Alexeev, D (author)
- Aulchenko, Y (author)
- Amininejad, L (author)
- Bouma, G (author)
- Hoentjen, F (author)
- Lowenberg, M (author)
- Oldenburg, B (author)
- Pierik, MJ (author)
- vander Meulen-de Jong, AE (author)
- van der Woude, CJ (author)
- Visschedijk, MC (author)
- Lathrop, M (author)
- Hugot, JP (author)
- Weersma, RK (author)
- De Vos, M (author)
- Franchimont, D (author)
- Vermeire, S (author)
- Kubo, M (author)
- Louis, E (author)
- Georges, M (author)
- Abraham, C (author)
- Achkar, JP (author)
- Ahmad, T (author)
- Ananthakrishnan, AN (author)
- Andersen, V (author)
- Anderson, CA (author)
- Andrews, JM (author)
- Annese, V (author)
- Aumais, G (author)
- Baidoo, L (author)
- Baldassano, RN (author)
- Bampton, PA (author)
- Barclay, M (author)
- Barrett, JC (author)
- Bayless, TM (author)
- Bethge, J (author)
- Bitton, A (author)
- Boucher, G (author)
- Brand, S (author)
- Brandt, B (author)
- Brant, SR (author)
- Buning, C (author)
- Chew, A (author)
- Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology(Swepub:oru)jshn (author)
- Cleynen, I (author)
- Cohain, A (author)
- Croft, A (author)
- Daly, MJ (author)
- D'Amato, MKarolinska Institutet (author)
- Danese, S (author)
- De Jong, D (author)
- Denapiene, G (author)
- Denson, LA (author)
- Devaney, KL (author)
- Dewit, O (author)
- D'Inca, R (author)
- Dubinsky, M (author)
- Duerr, RH (author)
- Edwards, C (author)
- Ellinghaus, D (author)
- Essers, J (author)
- Ferguson, LR (author)
- Festen, EA (author)
- Fleshner, P (author)
- Florin, T (author)
- Franke, A (author)
- Fransen, K (author)
- Gearry, R (author)
- Gieger, C (author)
- Glas, J (author)
- Goyette, P (author)
- Green, T (author)
- Griffiths, AM (author)
- Guthery, SL (author)
- Hakonarson, H (author)
- Halfvarson, J (author)
- Hanigan, K (author)
- Haritunians, T (author)
- Hart, A (author)
- Hawkey, C (author)
- Hayward, NK (author)
- Hedl, M (author)
- Henderson, P (author)
- Hu, XH (author)
- Huang, HL (author)
- Hui, KY (author)
- Imielinski, M (author)
- Ippoliti, A (author)
- Jonaitis, L (author)
- Jostins, L (author)
- Karlsen, TH (author)
- Kennedy, NA (author)
- Khan, MA (author)
- Kiudelis, G (author)
- Krishnaprasad, K (author)
- Kugathasan, S (author)
- Kupcinskas, L (author)
- Latiano, A (author)
- Laukens, D (author)
- Lawrance, IC (author)
- Lee, JC (author)
- Lees, CW (author)
- Leja, M (author)
- Van Limbergen, J (author)
- Lionetti, P (author)
- Liu, JZ (author)
- Mahy, G (author)
- Mansfield, J (author)
- Massey, D (author)
- Mathew, CG (author)
- McGovern, DPB (author)
- Milgrom, R (author)
- Mitrovic, M (author)
- Montgomery, GW (author)
- Mowat, C (author)
- Newman, W (author)
- Ng, A (author)
- Ng, SC (author)
- Ng, SME (author)
- Nikolaus, S (author)
- Ning, K (author)
- Nothen, M (author)
- Oikonomou, I (author)
- Palmieri, O (author)
- Parkes, M (author)
- Phillips, A (author)
- Ponsioen, CY (author)
- Potocnik, U (author)
- Prescott, NJ (author)
- Proctor, DD (author)
- Radford-Smith, G (author)
- Rahier, JF (author)
- Raychaudhuri, S (author)
- Regueiro, M (author)
- Rieder, F (author)
- Rioux, JD (author)
- Ripke, S (author)
- Roberts, R (author)
- Russell, RK (author)
- Sanderson, JD (author)
- Sans, M (author)
- Satsangi, J (author)
- Schadt, EE (author)
- Schreiber, S (author)
- Schulte, D (author)
- Schumm, LP (author)
- Scott, R (author)
- Seielstad, M (author)
- Sharma, Y (author)
- Silverberg, MS (author)
- Simms, LA (author)
- Skieceviciene, J (author)
- Spain, SL (author)
- Steinhart, AH (author)
- Stempak, JM (author)
- Stronati, L (author)
- Sventoraityte, J (author)
- Targan, SR (author)
- Taylor, KM (author)
- ter Velde, A (author)
- Torkvist, LKarolinska Institutet (author)
- Tremelling, M (author)
- van Sommeren, S (author)
- Vasiliauskas, E (author)
- Verspaget, HW (author)
- Walters, T (author)
- Wang, K (author)
- Wang, MH (author)
- Wei, Z (author)
- Whiteman, D (author)
- Wijmenga, C (author)
- Wilson, DC (author)
- Winkelmann, J (author)
- Xavier, RJ (author)
- Zhang, B (author)
- Zhang, CK (author)
- Zhang, H (author)
- Zhang, W (author)
- Zhao, HYDepartment of Biostatistics, School of Public Health, Yale University, New Haven CT, United States (author)
- Zhao, ZZ (author)
- Karolinska InstitutetUnit of Animal Genomics, WELBIO, GIGA-R, Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Science, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan (creator_code:org_t)
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- In:Nature communications: Springer Science and Business Media LLC9:1, s. 2427-2041-1723
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- Gearry, R
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- Halfvarson, J
- Hanigan, K
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- Hart, A
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- Hayward, NK
- Hedl, M
- Henderson, P
- Hu, XH
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- Hui, KY
- Imielinski, M
- Ippoliti, A
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- Jostins, L
- Karlsen, TH
- Kennedy, NA
- Khan, MA
- Kiudelis, G
- Krishnaprasad, K
- Kugathasan, S
- Kupcinskas, L
- Latiano, A
- Laukens, D
- Lawrance, IC
- Lee, JC
- Lees, CW
- Leja, M
- Van Limbergen, J
- Lionetti, P
- Liu, JZ
- Mahy, G
- Mansfield, J
- Massey, D
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- Potocnik, U
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- Rahier, JF
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- Russell, RK
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- Stempak, JM
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- Wilson, DC
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