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 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 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^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

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.

Originalsprog	Engelsk
Artikelnummer	15789
Tidsskrift	Nature Communications
Vol/bind	8
DOI	https://doi.org/10.1038/ncomms15789
Status	Udgivet - 6 jun. 2017

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10.1038/ncomms15789

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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., 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

@article{7bba67d3c6a84c69a05afadd39ded003,

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

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.",

author = "Snaevar Sigurdsson and Alexandersson, {Kristjan F.} and Patrick Sulem and Bjarke Feenstra and Steinunn Gudmundsdottir and Halldorsson, {Gisli H.} and Sigurgeir Olafsson and Asgeir Sigurdsson and Thorunn Rafnar and Thorgeir Thorgeirsson and Erik S{\o}rensen and Andreas Nordholm-Carstensen and Jakob Burcharth and Jens Andersen and J{\o}rgensen, {Henrik Stig} and Emma Possfelt-M{\o}ller and Henrik Ullum and Gudmar Thorleifsson and Gisli Masson and Unnur Thorsteinsdottir and Mads Melbye and Gudbjartsson, {Daniel F.} and Tryggvi Stefansson and Ingileif Jonsdottir and Kari Stefansson",

year = "2017",

month = jun,

day = "6",

doi = "10.1038/ncomms15789",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Sigurdsson, S, Alexandersson, KF, Sulem, P, Feenstra, B, Gudmundsdottir, S, Halldorsson, GH, Olafsson, S, Sigurdsson, A, Rafnar, T, Thorgeirsson, T, 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, bind 8, 15789. https://doi.org/10.1038/ncomms15789

TY - JOUR

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85020479917&partnerID=8YFLogxK

U2 - 10.1038/ncomms15789

DO - 10.1038/ncomms15789

M3 - Article

C2 - 28585551

AN - SCOPUS:85020479917

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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