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Fine-mapping inflammatory bowel disease loci to single-variant resolution

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Fine-mapping inflammatory bowel disease loci to single-variant resolution. / Huang, Hailiang; Fang, Ming; Jostins, Luke et al.
In: Nature, Vol. 547, No. 7662, 13.07.2017, p. 173-178.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Huang, H, Fang, M, Jostins, L, Umićević Mirkov, M, Boucher, G, Anderson, CA, Andersen, V, Cleynen, I, Cortes, A, Crins, F, D'Amato, M, Deffontaine, V, Dmitrieva, J, Docampo, E, Elansary, M, Farh, KK-H, Franke, A, Gori, A-S, Goyette, P, Halfvarson, J, Haritunians, T, Knight, J, Lawrance, IC, Lees, CW, Louis, E, Mariman, R, Meuwissen, T, Mni, M, Momozawa, Y, Parkes, M, Spain, SL, Théâtre, E, Trynka, G, Satsangi, J, van Sommeren, S, Vermeire, S, Xavier, RJ, Weersma, RK, Duerr, RH, Mathew, CG, Rioux, JD, McGovern, DPB, Cho, JH, Georges, M, Daly, MJ, Barrett, JC & International Inflammatory Bowel Disease Genetics Consortium 2017, 'Fine-mapping inflammatory bowel disease loci to single-variant resolution', Nature, vol. 547, no. 7662, pp. 173-178. https://doi.org/10.1038/nature22969

APA

Huang, H., Fang, M., Jostins, L., Umićević Mirkov, M., Boucher, G., Anderson, C. A., Andersen, V., Cleynen, I., Cortes, A., Crins, F., D'Amato, M., Deffontaine, V., Dmitrieva, J., Docampo, E., Elansary, M., Farh, K. K.-H., Franke, A., Gori, A.-S., Goyette, P., ... International Inflammatory Bowel Disease Genetics Consortium (2017). Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature, 547(7662), 173-178. https://doi.org/10.1038/nature22969

Vancouver

Huang H, Fang M, Jostins L, Umićević Mirkov M, Boucher G, Anderson CA et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature. 2017 Jul 13;547(7662):173-178. Epub 2017 Jun 28. doi: 10.1038/nature22969

Author

Huang, Hailiang ; Fang, Ming ; Jostins, Luke et al. / Fine-mapping inflammatory bowel disease loci to single-variant resolution. In: Nature. 2017 ; Vol. 547, No. 7662. pp. 173-178.

Bibtex

@article{4dcb191425634c2aae0501d7b0c8582f,
title = "Fine-mapping inflammatory bowel disease loci to single-variant resolution",
abstract = "Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.",
author = "Hailiang Huang and Ming Fang and Luke Jostins and {Umi{\'c}evi{\'c} Mirkov}, Ma{\v s}a and Gabrielle Boucher and Anderson, {Carl A} and Vibeke Andersen and Isabelle Cleynen and Adrian Cortes and Fran{\c c}ois Crins and Mauro D'Amato and Val{\'e}rie Deffontaine and Julia Dmitrieva and Elisa Docampo and Mahmoud Elansary and Farh, {Kyle Kai-How} and Andre Franke and Ann-Stephan Gori and Philippe Goyette and Jonas Halfvarson and Talin Haritunians and Jo Knight and Lawrance, {Ian C} and Lees, {Charlie W} and Edouard Louis and Rob Mariman and Theo Meuwissen and Myriam Mni and Yukihide Momozawa and Miles Parkes and Spain, {Sarah L} and Emilie Th{\'e}{\^a}tre and Gosia Trynka and Jack Satsangi and {van Sommeren}, Suzanne and Severine Vermeire and Xavier, {Ramnik J} and Weersma, {Rinse K} and Duerr, {Richard H} and Mathew, {Christopher G} and Rioux, {John D} and McGovern, {Dermot P B} and Cho, {Judy H} and Michel Georges and Daly, {Mark J} and Barrett, {Jeffrey C} and {International Inflammatory Bowel Disease Genetics Consortium}",
year = "2017",
month = jul,
day = "13",
doi = "10.1038/nature22969",
language = "English",
volume = "547",
pages = "173--178",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7662",

}

RIS

TY - JOUR

T1 - Fine-mapping inflammatory bowel disease loci to single-variant resolution

AU - Huang, Hailiang

AU - Fang, Ming

AU - Jostins, Luke

AU - Umićević Mirkov, Maša

AU - Boucher, Gabrielle

AU - Anderson, Carl A

AU - Andersen, Vibeke

AU - Cleynen, Isabelle

AU - Cortes, Adrian

AU - Crins, François

AU - D'Amato, Mauro

AU - Deffontaine, Valérie

AU - Dmitrieva, Julia

AU - Docampo, Elisa

AU - Elansary, Mahmoud

AU - Farh, Kyle Kai-How

AU - Franke, Andre

AU - Gori, Ann-Stephan

AU - Goyette, Philippe

AU - Halfvarson, Jonas

AU - Haritunians, Talin

AU - Knight, Jo

AU - Lawrance, Ian C

AU - Lees, Charlie W

AU - Louis, Edouard

AU - Mariman, Rob

AU - Meuwissen, Theo

AU - Mni, Myriam

AU - Momozawa, Yukihide

AU - Parkes, Miles

AU - Spain, Sarah L

AU - Théâtre, Emilie

AU - Trynka, Gosia

AU - Satsangi, Jack

AU - van Sommeren, Suzanne

AU - Vermeire, Severine

AU - Xavier, Ramnik J

AU - Weersma, Rinse K

AU - Duerr, Richard H

AU - Mathew, Christopher G

AU - Rioux, John D

AU - McGovern, Dermot P B

AU - Cho, Judy H

AU - Georges, Michel

AU - Daly, Mark J

AU - Barrett, Jeffrey C

AU - International Inflammatory Bowel Disease Genetics Consortium

PY - 2017/7/13

Y1 - 2017/7/13

N2 - Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

AB - Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.

U2 - 10.1038/nature22969

DO - 10.1038/nature22969

M3 - Journal article

C2 - 28658209

VL - 547

SP - 173

EP - 178

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7662

ER -