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Discovery and syste...
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Aragam, KGBroad Institute
(author)
Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-12-06
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Springer Science and Business Media LLC,2022
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:152776091
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http://kipublications.ki.se/Default.aspx?queryparsed=id:152776091URI
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https://doi.org/10.1038/s41588-022-01233-6DOI
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https://lup.lub.lu.se/record/50f86865-802b-4787-a3f5-a6548a1dfbaaURI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Jiang, T
(author)
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Goel, A
(author)
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Kanoni, S
(author)
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Wolford, BN
(author)
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Atri, DS
(author)
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Weeks, EM
(author)
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Wang, M
(author)
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Hindy, GeorgeQatar University(Swepub:lu)med-ghu
(author)
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Zhou, W
(author)
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Grace, C
(author)
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Roselli, C
(author)
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Marston, NA
(author)
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Kamanu, FK
(author)
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Surakka, I
(author)
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Venegas, LM
(author)
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Sherliker, P
(author)
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Koyama, SatoshiRIKEN Center for Integrative Medical Sciences(Swepub:lu)sa2525ko
(author)
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Ishigaki, K
(author)
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Asvold, BO
(author)
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Brown, MR
(author)
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Brumpton, B
(author)
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de Vries, PS
(author)
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Giannakopoulou, O
(author)
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Giardoglou, P
(author)
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Gudbjartsson, DF
(author)
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Guldener, U
(author)
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Haider, SMI
(author)
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Helgadottir, A
(author)
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Ibrahim, M
(author)
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Kastrati, A
(author)
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Kessler, T
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Kyriakou, T
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Konopka, T
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Li, L
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Ma, L
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Meitinger, T
(author)
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Mucha, S
(author)
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Munz, M
(author)
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Murgia, F
(author)
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Nielsen, JB
(author)
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Nothen, MM
(author)
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Pang, S
(author)
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Reinberger, T
(author)
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Schnitzler, G
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Smedley, D
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Thorleifsson, G
(author)
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von Scheidt, M
(author)
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Ulirsch, JC
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Arnar, DO
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Burtt, NP
(author)
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Costanzo, MC
(author)
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Flannick, J
(author)
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Ito, K
(author)
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Jang, DK
(author)
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Kamatani, Y
(author)
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Khera, AV
(author)
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Komuro, I
(author)
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Kullo, IJ
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Lotta, LA
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Nelson, CP
(author)
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Roberts, R
(author)
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Thorgeirsson, G
(author)
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Thorsteinsdottir, U
(author)
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Webb, TR
(author)
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Baras, A
(author)
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Bjorkegren, JLMKarolinska Institutet
(author)
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Boerwinkle, E
(author)
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Dedoussis, G
(author)
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Holm, H
(author)
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Hveem, K
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome
(author)
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Morrison, AC
(author)
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Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
(author)
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Rallidis, LS
(author)
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Ruusalepp, A
(author)
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Sabatine, MS
(author)
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Stefansson, K
(author)
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Zalloua, P
(author)
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Ellinor, PT
(author)
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Farrall, M
(author)
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Danesh, J
(author)
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Ruff, CT
(author)
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Finucane, HK
(author)
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Hopewell, JC
(author)
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Clarke, R
(author)
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Gupta, RM
(author)
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Erdmann, J
(author)
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Samani, NJ
(author)
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Schunkert, H
(author)
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Watkins, H
(author)
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Willer, CJ
(author)
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Deloukas, P
(author)
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Kathiresan, S
(author)
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Butterworth, ASUniversity of Cambridge
(author)
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Broad InstituteQatar University
(creator_code:org_t)
Related titles
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In:Nature genetics: Springer Science and Business Media LLC54:12, s. 1803-18151546-17181061-4036
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Find in a library
To the university's database
- By the author/editor
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Aragam, KG
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Jiang, T
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Goel, A
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Kanoni, S
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Wolford, BN
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Atri, DS
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show more...
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Weeks, EM
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Wang, M
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Hindy, George
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Zhou, W
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Grace, C
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Roselli, C
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Marston, NA
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Kamanu, FK
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Surakka, I
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Venegas, LM
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Sherliker, P
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Koyama, Satoshi
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Ishigaki, K
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Asvold, BO
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Brown, MR
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Brumpton, B
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de Vries, PS
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Giannakopoulou, ...
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Giardoglou, P
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Gudbjartsson, DF
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Guldener, U
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Haider, SMI
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Helgadottir, A
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Ibrahim, M
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Kastrati, A
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Kessler, T
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Kyriakou, T
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Konopka, T
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Li, L
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Ma, L
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Meitinger, T
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Mucha, S
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Munz, M
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Murgia, F
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Nielsen, JB
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Nothen, MM
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Pang, S
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Reinberger, T
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Schnitzler, G
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Smedley, D
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Thorleifsson, G
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von Scheidt, M
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Ulirsch, JC
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Arnar, DO
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Burtt, NP
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Costanzo, MC
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Flannick, J
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Ito, K
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Jang, DK
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Kamatani, Y
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Khera, AV
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Komuro, I
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Kullo, IJ
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Lotta, LA
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Nelson, CP
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Roberts, R
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Thorgeirsson, G
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Thorsteinsdottir ...
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Webb, TR
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Baras, A
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Bjorkegren, JLM
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Boerwinkle, E
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Dedoussis, G
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Holm, H
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Hveem, K
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Melander, Olle
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Morrison, AC
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Orho-Melander, M ...
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Rallidis, LS
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Ruusalepp, A
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Sabatine, MS
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Stefansson, K
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Zalloua, P
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Ellinor, PT
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Farrall, M
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Danesh, J
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Ruff, CT
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Finucane, HK
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Hopewell, JC
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Clarke, R
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Gupta, RM
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Erdmann, J
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Samani, NJ
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Schunkert, H
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Watkins, H
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Willer, CJ
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Deloukas, P
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Kathiresan, S
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Butterworth, AS
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature genetics
- By the university
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Karolinska Institutet
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Lund University