GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

被引：109

作者：

Franceschini, Nora ^{[1
]}

Giambartolomei, Claudia ^{[2
]}

de Vries, Paul S. ^{[3
]}

Finan, Chris ^{[4
]}

Bis, Joshua C. ^{[5
]}

Huntley, Rachael P. ^{[4
]}

Lovering, Ruth C. ^{[4
]}

Tajuddin, Salman M. ^{[6
]}

Winkler, Thomas W. ^{[7
]}

Graff, Misa ^{[1
]}

Kavousi, Maryam ^{[8
]}

Dale, Caroline ^{[9
]}

Smith, Albert V. ^{[10
,11
]}

Hofer, Edith ^{[12
,13
]}

van Leeuwen, Elisabeth M. ^{[8
]}

Nolte, Ilja M. ^{[14
]}

Lu, Lingyi ^{[15
]}

Scholz, Markus ^{[16
,17
]}

Sargurupremraj, Muralidharan ^{[18
]}

Pitkanen, Niina ^{[19
]}

Franzen, Oscar ^{[20
,21
]}

Joshi, Peter K. ^{[22
]}

Noordam, Raymond ^{[23
]}

Marioni, Riccardo E. ^{[24
,25
]}

Hwang, Shih-Jen ^{[26
,27
]}

Musani, Solomon K. ^{[28
]}

Schminke, Ulf ^{[29
]}

Palmas, Walter ^{[30
]}

Isaacs, Aaron ^{[8
,31
]}

Correa, Adolfo ^{[28
]}

Zonderman, Alan B. ^{[6
]}

Hofman, Albert ^{[8
,32
]}

Teumer, Alexander ^{[33
,34
]}

Cox, Amanda J. ^{[35
,36
]}

Uitterlinden, Andre G. ^{[8
,37
]}

Wong, Andrew ^{[38
]}

Smit, Andries J. ^{[39
]}

Newman, Anne B. ^{[40
,41
]}

Britton, Annie ^{[42
]}

Ruusalepp, Arno ^{[21
,43
,44
]}

Sennblad, Bengt ^{[45
,46
]}

Hedblad, Bo ^{[47
]}

Pasaniuc, Bogdan ^{[2
,48
]}

Penninx, Brenda W. ^{[49
]}

Langefeld, Carl D. ^{[15
]}

Wassel, Christina L. ^{[50
]}

Tzourio, Christophe ^{[18
]}

Fava, Cristiano ^{[47
,51
]}

Baldassarre, Damiano ^{[52
,53
]}

O'Leary, Daniel H. ^{[54
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA

[2] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[3] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA

[4] UCL, Inst Cardiovasc Sci, London WC1 6BT, England

[5] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[6] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA

[7] Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany

[8] Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands

[9] UCL, Inst Hlth Informat, London WC1E 6BT, England

[10] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[11] Univ Iceland, IS-101 Reykjavik, Iceland

[12] Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria

[13] Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria

[14] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands

[15] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA

[16] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany

[17] Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany

[18] Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France

[19] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland

[20] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

[21] Clin Gene Networks AB, S-10462 Stockholm, Sweden

[22] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland

[23] Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands

[24] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

[25] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland

[26] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Framingham, MA 01702 USA

[27] NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA

[28] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

[29] Univ Med Greifswald, Dept Neurol, D-17475 Greifswald, Germany

[30] Columbia Univ, Dept Med, New York, NY 10032 USA

[31] Maastricht Univ, CARIM Sch Cardiovasc Dis, Maastricht Ctr Syst Biol MaCSBio, Dept Biochem, NL-6229 Maastricht, Netherlands

[32] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[33] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany

[34] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany

[35] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 25157 USA

[36] Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld 4222, Australia

[37] Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands

[38] UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England

[39] Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-2300 Groningen, Netherlands

[40] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA

[41] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA

[42] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England

[43] Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia

[44] Tartu Univ Hosp, Dept Cardiac Surg, EE-51010 Tartu, Estonia

[45] Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden

[46] Uppsala Univ, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Dept Cell & Mol Biol, S-75108 Uppsala, Sweden

[47] Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden

[48] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[49] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci Campus Amste, Department Psychiat, NL-1081 HL Amsterdam, Netherlands

[50] Premier Inc, Appl Sci, Charlotte, NC 28277 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; INTEGRATIVE ANALYSIS; GENE-PRODUCT; METAANALYSIS; VARIANTS; HEART;

D O I：

10.1038/s41467-018-07340-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

引用

页数：14

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← 1 2 3 4 →

共 33 条

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Arner, Erik ;

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Glatz, Dagmar ;

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Kelley, Ryan ;

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SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (383)

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