Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis

Snaevar Sigurdsson; Kristjan F Alexandersson; Patrick Sulem; Bjarke Feenstra; Steinunn Gudmundsdottir; Gisli H. Halldorsson; Sigurgeir Olafsson; Asgeir Sigurdsson; Thorunn Rafnar; Thorgeir E Thorgeirsson; Erik Sørensen; Andreas Nordholm-Carstensen; Jakob Burcharth; Jens Andersen; Henrik Stig Jørgensen; Emma Possfelt-Møller; Henrik Ullum; Gudmar Thorleifsson; Gisli Masson; Unnur Thorsteinsdottir; Mads Melbye; Daniel F Gudbjartsson; Tryggvi Stefansson; Ingileif Jonsdottir; Kari Stefansson

doi:10.1038/ncomms15789

Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis

Snaevar Sigurdsson, Kristjan F Alexandersson, Patrick Sulem, Bjarke Feenstra, Steinunn Gudmundsdottir, Gisli H. Halldorsson, Sigurgeir Olafsson, Asgeir Sigurdsson, Thorunn Rafnar, Thorgeir E Thorgeirsson, Erik Sørensen, Andreas Nordholm-Carstensen, Jakob Burcharth, Jens Andersen, Henrik Stig Jørgensen, Emma Possfelt-Møller, Henrik Ullum, Gudmar Thorleifsson, Gisli Masson, Unnur ThorsteinsdottirMads Melbye, Daniel F Gudbjartsson, Tryggvi Stefansson, Ingileif Jonsdottir, Kari Stefansson

Department of Clinical Medicine

32 Citations (Scopus)

Abstract

Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-Activating protein 15; rs4662344-T: P=1.9 × 10 â '18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10 â '10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10 â '11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

Original language	English
Article number	15789
Journal	Nature Communications
Volume	8
Number of pages	7
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms15789
Publication status	Published - 6 Jun 2017

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Sigurdsson, S., Alexandersson, K. F., Sulem, P., Feenstra, B., Gudmundsdottir, S., Halldorsson, G. H., Olafsson, S., Sigurdsson, A., Rafnar, T., Thorgeirsson, T. E., Sørensen, E., Nordholm-Carstensen, A., Burcharth, J., Andersen, J., Jørgensen, H. S., Possfelt-Møller, E., Ullum, H., Thorleifsson, G., Masson, G., ... Stefansson, K. (2017). Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis. Nature Communications, 8, [15789]. https://doi.org/10.1038/ncomms15789

Sigurdsson, S, Alexandersson, KF, Sulem, P, Feenstra, B, Gudmundsdottir, S, Halldorsson, GH, Olafsson, S, Sigurdsson, A, Rafnar, T, Thorgeirsson, TE, Sørensen, E, Nordholm-Carstensen, A, Burcharth, J, Andersen, J, Jørgensen, HS, Possfelt-Møller, E, Ullum, H, Thorleifsson, G, Masson, G, Thorsteinsdottir, U, Melbye, M, Gudbjartsson, DF, Stefansson, T, Jonsdottir, I & Stefansson, K 2017, 'Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis', Nature Communications, vol. 8, 15789. https://doi.org/10.1038/ncomms15789

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abstract = "Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-Activating protein 15; rs4662344-T: P=1.9 × 10 {\^a} '18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10 {\^a} '10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10 {\^a} '11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.",

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T1 - Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis

AU - Sigurdsson, Snaevar

AU - Alexandersson, Kristjan F

AU - Sulem, Patrick

AU - Feenstra, Bjarke

AU - Gudmundsdottir, Steinunn

AU - Halldorsson, Gisli H.

AU - Olafsson, Sigurgeir

AU - Sigurdsson, Asgeir

AU - Rafnar, Thorunn

AU - Thorgeirsson, Thorgeir E

AU - Sørensen, Erik

AU - Nordholm-Carstensen, Andreas

AU - Burcharth, Jakob

AU - Andersen, Jens

AU - Jørgensen, Henrik Stig

AU - Possfelt-Møller, Emma

AU - Ullum, Henrik

AU - Thorleifsson, Gudmar

AU - Masson, Gisli

AU - Thorsteinsdottir, Unnur

AU - Melbye, Mads

AU - Gudbjartsson, Daniel F

AU - Stefansson, Tryggvi

AU - Jonsdottir, Ingileif

AU - Stefansson, Kari

PY - 2017/6/6

Y1 - 2017/6/6

N2 - Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-Activating protein 15; rs4662344-T: P=1.9 × 10 â '18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10 â '10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10 â '11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

AB - Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-Activating protein 15; rs4662344-T: P=1.9 × 10 â '18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10 â '10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10 â '11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study.

KW - Journal Article

U2 - 10.1038/ncomms15789

DO - 10.1038/ncomms15789

M3 - Journal article

C2 - 28585551

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15789

ER -

Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis

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