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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
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- Momozawa, Y (author)
- Unit 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
- Dmitrieva, J (author)
- Theatre, E (author)
- show more...
- 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)
- 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)
- Cleynen, I (author)
- Cohain, A (author)
- Croft, A (author)
- Daly, MJ (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)
- 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, ZZ (author)
- show less...
- (creator_code:org_t)
- 2018-06-21
- 2018
- English.
- In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
- Momozawa, Y
- Dmitrieva, J
- Theatre, E
- Deffontaine, V
- Rahmouni, S
- Charloteaux, B
- show more...
- Crins, F
- Docampo, E
- Elansary, M
- Gori, AS
- Lecut, C
- Mariman, R
- Mni, M
- Oury, C
- Altukhov, I
- Alexeev, D
- Aulchenko, Y
- Amininejad, L
- Bouma, G
- Hoentjen, F
- Lowenberg, M
- Oldenburg, B
- Pierik, MJ
- vander Meulen-de ...
- van der Woude, C ...
- Visschedijk, MC
- Lathrop, M
- Hugot, JP
- Weersma, RK
- De Vos, M
- Franchimont, D
- Vermeire, S
- Kubo, M
- Louis, E
- Georges, M
- Abraham, C
- Achkar, JP
- Ahmad, T
- Ananthakrishnan, ...
- Andersen, V
- Anderson, CA
- Andrews, JM
- Annese, V
- Aumais, G
- Baidoo, L
- Baldassano, RN
- Bampton, PA
- Barclay, M
- Barrett, JC
- Bayless, TM
- Bethge, J
- Bitton, A
- Boucher, G
- Brand, S
- Brandt, B
- Brant, SR
- Buning, C
- Chew, A
- Halfvarson, Jona ...
- Cleynen, I
- Cohain, A
- Croft, A
- Daly, MJ
- D'Amato, M
- Danese, S
- De Jong, D
- Denapiene, G
- Denson, LA
- Devaney, KL
- Dewit, O
- D'Inca, R
- Dubinsky, M
- Duerr, RH
- Edwards, C
- Ellinghaus, D
- Essers, J
- Ferguson, LR
- Festen, EA
- Fleshner, P
- Florin, T
- Franke, A
- Fransen, K
- Gearry, R
- Gieger, C
- Glas, J
- Goyette, P
- Green, T
- Griffiths, AM
- Guthery, SL
- Hakonarson, H
- Halfvarson, J
- Hanigan, K
- Haritunians, T
- Hart, A
- Hawkey, C
- Hayward, NK
- Hedl, M
- Henderson, P
- Hu, XH
- Huang, HL
- Hui, KY
- Imielinski, M
- Ippoliti, A
- Jonaitis, L
- 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
- Mathew, CG
- McGovern, DPB
- Milgrom, R
- Mitrovic, M
- Montgomery, GW
- Mowat, C
- Newman, W
- Ng, A
- Ng, SC
- Ng, SME
- Nikolaus, S
- Ning, K
- Nothen, M
- Oikonomou, I
- Palmieri, O
- Parkes, M
- Phillips, A
- Ponsioen, CY
- Potocnik, U
- Prescott, NJ
- Proctor, DD
- Radford-Smith, G
- Rahier, JF
- Raychaudhuri, S
- Regueiro, M
- Rieder, F
- Rioux, JD
- Ripke, S
- Roberts, R
- Russell, RK
- Sanderson, JD
- Sans, M
- Satsangi, J
- Schadt, EE
- Schreiber, S
- Schulte, D
- Schumm, LP
- Scott, R
- Seielstad, M
- Sharma, Y
- Silverberg, MS
- Simms, LA
- Skieceviciene, J
- Spain, SL
- Steinhart, AH
- Stempak, JM
- Stronati, L
- Sventoraityte, J
- Targan, SR
- Taylor, KM
- ter Velde, A
- Torkvist, L
- Tremelling, M
- van Sommeren, S
- Vasiliauskas, E
- Verspaget, HW
- Walters, T
- Wang, K
- Wang, MH
- Wei, Z
- Whiteman, D
- Wijmenga, C
- Wilson, DC
- Winkelmann, J
- Xavier, RJ
- Zhang, B
- Zhang, CK
- Zhang, H
- Zhang, W
- Zhao, HY
- Zhao, ZZ
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medical Genetics
- Articles in the publication
- Nature communica ...
- By the university
- Karolinska Institutet
- Örebro University
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