Large-scale gene-centric analysis identifies novel variants for coronary artery disease.
Details
Serval ID
serval:BIB_35AD48005E04
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Large-scale gene-centric analysis identifies novel variants for coronary artery disease.
Journal
Plos Genetics
Working group(s)
IBC 50K CAD Consortium
Contributor(s)
Butterworth AS., Braund PS., Farrall M., Hardwick RJ., Saleheen D., Peden JF., Soranzo N., Chambers JC., Sivapalaratnam S., Kleber ME., Keating B., Qasim A., Klopp N., Erdmann J., Assimes TL., Ball SG., Balmforth AJ., Barnes TA., Basart H., Baumert J., Bezzina CR., Boerwinkle E., Boehm BO., Brocheton J., Bugert P., Cambien F., Clarke R., Codd V., Collins R., Couper D., Cupples LA., de Jong JS. , Diemert P., Ejebe K., Elbers CC., Elliott P., Fornage M., Franzosi MG., Frossard P., Garner S., Goel A., Goodall AH., Hengstenberg C., Hunt SE., Kastelein JJ., Klungel OH., Klüter H., Koch K., König IR., Kooner AS., Laaksonen R., Lathrop M., Li M., Liu K., McPherson R., Musameh MD., Musani S., Nelson CP., O'Donnell CJ., Ongen H., Papanicolaou G., Peters A., Peters BJ., Potter S., Psaty BM., Qu L., Rader DJ., Rasheed A., Rice C., Scott J., Seedorf U., Sehmi JS., Sotoodehnia N., Stark K., Stephens J., van der Schoot CE. , van der Schouw YT. , Thorsteinsdottir U., Tomaszewski M., van der Harst P., Vasan RS., Wilde AA., Willenborg C., Winkelmann BR., Zaidi M., Zhang W., Ziegler A., de Bakker PI. , Koenig W., Mätz W., Trip MD., Reilly MP., Kathiresan S., Schunkert H., Hamsten A., Hall AS., Kooner JS., Thompson SG., Thompson JR., Deloukas P., Ouwehand WH., Watkins H., Danesh J., Samani NJ., Barnes T., Rafelt S., Codd V., Tomaszewski M., Ouwehand WH., Bruinsma N., Dekker LR., Henriques JP., Koch KT., de Winter RJ. , Alings M., Allaart CF., Gorgels AP., Verheugt FW., Braund PS., Thompson JR., Samani NJ., Mueller M., Meisinger C., DerOhannessian S., Mehta NN., Ferguson J., Hakonarson H., Matthai W., Wilensky R., Hopewell JC., Parish S., Linksted P., Notman J., Gonzalez H., Young A., Ostley T., Munday A., Goodwin N., Verdon V., Shah S., Cobb L., Edwards C., Mathews C., Gunter R., Benham J., Davies C., Cobb M., Cobb L., Crowther J., Richards A., Silver M., Tochlin S., Mozley S., Clark S., Radley M., Kourellias K., Silveira A., Söderholm B., Olsson P., Barlera S., Tognoni G., Rust S., Assmann G., Heath S., Zelenika D., Gut I., Green F., Farrall M., Peden J., Goel A., Ongen H., Franzosi MG., Lathrop M., Seedorf U., Clarke R., Collins R., Hamsten A., Watkins H., Aly A., Anner K., Björklund K., Blomgren G., Cederschiöld B., Danell-Toverud K., Eriksson P., Grundstedt U., Hamsten A., Heinonen M., Hellénius ML., van't Hooft F., Husman K., Lagercrantz J., Larsson A., Larsson M., Mossfeldt M., Mälarstig A., Olsson G., Sabater-Lleal M., Sennblad B., Silveira A., Strawbridge R., Söderholm B., Öhrvik J., Zaman KS., Mallick NH., Azhar M., Samad A., Ishaq M., Shah N., Samuel M., Schunkert H., König IR., Kathiresan S., Reilly M., Assimes TL., Holm H., Preuss M., Stewart AF., Barbalic M., Gieger C., Absher D., Aherrahrou Z., Allayee H., Altshuler D., Anand S., Andersen K., Anderson JL., Ardissino D., Ball SG., Balmforth AJ., Barnes TA., Becker LC., Becker DM., Berger K., Bis JC., Boekholdt SM., Boerwinkle E., Braund PS., Brown MJ., Burnett MS., Buysschaert I., Carlquist JF., Chen L., Codd V., Davies RW., Dedoussis G., Dehghan A., Demissie S., Devaney J., Do R., Doering A., El Mokhtari NE. , Ellis SG., Elosua R., Engert JC., Epstein S., de Faire U., Fischer M., Folsom AR., Freyer J., Gigante B., Girelli D., Gretarsdottir S., Gudnason V., Gulcher JR., Tennstedt S., Halperin E., Hammond N., Hazen SL., Hofman A., Horne BD., Illig T., Iribarren C., Jones GT., Jukema JW., Kaiser MA., Kaplan LM., Kastelein JJ., Khaw KT., Knowles JW., Kolovou G., Kong A., Laaksonen R., Lambrechts D., Leander K., Li M., Lieb W., Diemert P., Lettre G., Loley C., Lotery AJ., Mannucci PM., Maouche S., Martinelli N., McKeown PP., Meisinger C., Meitinger T., Melander O., Merlini PA., Mooser V., Morgan T., Mühleisen TW., Muhlestein JB., Musunuru K., Nahrstaedt J., Nelson CP., Nöthen MM., Olivieri O., Peyvandi F., Patel RS., Patterson CC., Peters A., Qu L., Quyyumi AA., Rader DJ., Rallidis LS., Rice C., Rosendaal FR., Rubin D., Salomaa V., Sampietro ML., Sandhu MS., Schadt E., Schäfer A., Schillert A., Schreiber S., Schrezenmeir J., Schwartz SM., Siscovick DS., Sivananthan M., Sivapalaratnam S., Smith AV., Smith TB., Snoep JD., Soranzo N., Spertus JA., Stark K., Stefansson K., Stirrups K., Stoll M., Tang WH., Thorgeirsson G., Thorleifsson G., Tomaszewski M., Uitterlinden AG., van Rij AM. , Voight BF., Wareham NJ., AWells G., Wichmann HE., Willenborg C., Witteman JC., Wright BJ., Ye S., Ziegler A., Cambien F., Goodall AH., Cupples LA., Quertermous T., März W., Hengstenberg C., Blankenberg S., Ouwehand WH., Hall AS., Deloukas P., Thorsteinsdottir U., Roberts R., Thompson JR., O'Donnell CJ., McPherson R., Erdmann J., Samani NJ., Onland-Moret NC., van Setten J., de Bakker PI. , Verschuren WM., Boer JM., Wijmenga C., Hofker MH., Maitland-van der Zee AH. , de Boer A., Grobbee DE., Attwood T., Belz S., Braund P., Cambien F., Cooper J., Crisp-Hihn A., Diemert P., Deloukas P., Foad N., Erdmann J., Goodall AH., Gracey J., Gray E., Gwilliams R., Heimerl S., Hengstenberg C., Jolley J., Krishnan U., Lloyd-Jones H., Lugauer I., Lundmark P., Maouche S., Moore JS., Muir D., Murray E., Nelson CP., Neudert J., Niblett D., O'Leary K., Ouwehand WH., Pollard H., Rankin A., Rice CM., Sager H., Samani NJ., Sambrook J., Schmitz G., Scholz M., Schroeder L., Schunkert H., Syvannen AC., Tennstedt S., Wallace C.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2011
Volume
7
Number
9
Pages
e1002260
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.
Keywords
Adult, Aged, Alleles, Asian Continental Ancestry Group/genetics, Case-Control Studies, Coronary Artery Disease/genetics, European Continental Ancestry Group/genetics, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk
Pubmed
Web of science
Open Access
Yes
Create date
22/03/2012 10:44
Last modification date
20/08/2019 14:23
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