Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

被引：155

作者：

Gretarsdottir, Solveig ^{[1
]}

Baas, Annette F. ^{[2
,3
]}

Thorleifsson, Gudmar ^{[1
]}

Holm, Hilma ^{[1
]}

den Heijer, Martin ^{[4
,5
]}

de Vries, Jean-Paul P. M. ^{[6
]}

Kranendonk, Steef E. ^{[7
]}

Zeebregts, Clark J. A. M. ^{[8
]}

van Sterkenburg, Steven M. ^{[9
]}

Geelkerken, Robert H. ^{[10
]}

van Rij, Andre M. ^{[11
]}

Williams, Michael J. A. ^{[12
]}

Boll, Albert P. M. ^{[13
]}

Kostic, Jelena P. ^{[1
]}

Jonasdottir, Adalbjorg ^{[1
]}

Jonasdottir, Aslaug ^{[1
]}

Walters, G. Bragi ^{[1
]}

Masson, Gisli ^{[1
]}

Sulem, Patrick ^{[1
]}

Saemundsdottir, Jona ^{[1
]}

Mouy, Magali ^{[1
]}

Magnusson, Kristinn P. ^{[14
]}

Tromp, Gerard ^{[15
]}

Elmore, James R. ^{[16
]}

Sakalihasan, Natzi ^{[17
]}

Limet, Raymond ^{[17
]}

Defraigne, Jean-Olivier ^{[17
]}

Ferrell, Robert E. ^{[18
]}

Ronkainen, Antti ^{[19
]}

Ruigrok, Ynte M. ^{[20
]}

Wijmenga, Cisca ^{[21
,22
]}

Grobbee, Diederick E. ^{[3
]}

Shah, Svati H. ^{[23
,24
]}

Granger, Christopher B. ^{[23
,25
]}

Quyyumi, Arshed A. ^{[26
]}

Vaccarino, Viola ^{[26
]}

Patel, Riyaz S. ^{[26
,27
]}

Zafari, A. Maziar ^{[26
,28
]}

Levey, Allan I. ^{[26
]}

Austin, Harland ^{[29
]}

Girelli, Domenico ^{[30
]}

Pignatti, Pier Franco ^{[31
]}

Olivieri, Oliviero ^{[30
]}

Martinelli, Nicola ^{[30
]}

Malerba, Giovanni ^{[31
]}

Trabetti, Elisabetta ^{[31
]}

Becker, Lewis C. ^{[32
]}

Becker, Diane M. ^{[32
]}

Reilly, Muredach P. ^{[33
]}

Rader, Daniel J. ^{[33
]}

机构：

[1] DeCODE Genet, Populat Genom, Reykjavik, Iceland

[2] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands

[5] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands

[6] St Antonius Hosp, Dept Vasc Surg, Nieuwegein, Netherlands

[7] TweeSteden Hosp Tilburg, Dept Surg, Tilburg, Netherlands

[8] Univ Med Ctr Groningen, Dept Surg, NL-9713 AV Groningen, Netherlands

[9] Locat Rijnstate, Alysis Zorggroep, Div Vasc Surg, Dept Surg, Arnhem, Netherlands

[10] Med Spectrum Twente, Dept Surg, Enschede, Netherlands

[11] Univ Otago, Dunedin Sch Med, Dept Surg, Dunedin, New Zealand

[12] Univ Otago, Dunedin Sch Med, Dept Med, Dunedin, New Zealand

[13] Canisius Wilhelmina Hosp Nijmegen, Dept Surg, Nijmegen, Netherlands

[14] Univ Akureyri, Borgir Vid Nordurslod, Akureyri, Iceland

[15] Weis Ctr Res, Geisinger Clin, Weis Ctr Res, Danville, PA 17822 USA

[16] Weis Ctr Res, Geisinger Clin, Dept Vasc Surg, Danville, PA 17822 USA

[17] Univ Liege, Liege, Belgium

[18] Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA

[19] Kuopio Univ Hosp, Dept Neurosurg, SF-70210 Kuopio, Finland

[20] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands

[21] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[22] Univ Groningen, Groningen, Netherlands

[23] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[24] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA

[25] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA

[26] Emory Univ, Sch Med, Atlanta, GA USA

[27] Cardiff Univ, Cardiff, S Glam, Wales

[28] Atlanta Vet Affairs Med Ctr, Decatur, GA USA

[29] Emory Univ, Sch Publ Hlth, Atlanta, GA USA

[30] Univ Verona, Dept Med, Sect Internal Med, I-37100 Verona, Italy

[31] Univ Verona, Dept Life & Reprod Sci, Sect Biol & Genet, I-37100 Verona, Italy

[32] Johns Hopkins Univ, Sch Med, Johns Hopkins GeneSTAR Res Program, Baltimore, MD USA

[33] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[34] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria

[35] Viborg Hosp, Vasc Res Unit, Viborg, Denmark

[36] Skaane Univ Hosp, Vasc Ctr, Malmo, Sweden

[37] Catholic Univ, Lab Vasc Biol & Genet, A Gemelli Univ Hosp, Sch Med,Dept Med, Rome, Italy

[38] Tufts Univ, Sch Med, Dept Med, Div Cardiovasc Res,Caritas St Elizabeths Med Ctr, Boston, MA 02111 USA

[39] Ottawa Hosp, Dept Med, Ottawa, ON, Canada

[40] Ottawa Hosp, Div Hematol, Ottawa, ON, Canada

[41] Univ Ottawa, Fac Med, Ottawa, ON, Canada

[42] Ottawa Hosp Res Inst, Ottawa, ON, Canada

[43] Univ Murcia, Dept Med, Ctr Reg Hemodonac, Murcia, Spain

[44] Santa Creu & St Pau Hosp, Hemostasia & Thrombosis Unit, Barcelona, Spain

[45] Hosp La Fe, Res Ctr, E-46009 Valencia, Spain

[46] Hagedorn Res Inst, Gentofte, Denmark

[47] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[48] Univ Copenhagen, Fac Hlth Sci, DK-1168 Copenhagen, Denmark

[49] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[50] Univ So Denmark, Odense, Denmark

来源：

NATURE GENETICS | 2010年 / 42卷 / 08期

基金：

美国国家卫生研究院; 瑞典研究理事会; 英国医学研究理事会;

关键词：

VENOUS THROMBOEMBOLISM; MYOCARDIAL-INFARCTION; FAMILY-HISTORY; LOCUS; RISK; HOMEOSTASIS; ARTERIAL; DISEASE; LINKAGE; 9P21;

D O I：

10.1038/ng.622

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

引用

页码：692 / U71

页数：7

共 37 条

[31] Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion [J].