Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mahajan:2018:10.1038/s41588-018-0084-1,
author = {Mahajan, A and Wessel, J and Willems, SM and Zhao, W and Robertson, NR and Chu, AY and Gan, W and Kitajima, H and Taliun, D and Rayner, NW and Guo, X and Lu, Y and Li, M and Jensen, RA and Hu, Y and Huo, S and Lohman, KK and Zhang, W and Cook, JP and Prins, BP and Flannick, J and Grarup, N and Trubetskoy, VV and Kravic, J and Kim, YJ and Rybin, DV and Yaghootkar, H and Mueller-Nurasyid, M and Meidtner, K and Li-Gao, R and Varga, TV and Marten, J and Li, J and Smith, AV and An, P and Ligthart, S and Gustafsson, S and Malerba, G and Demirkan, A and Tajes, JF and Steinthorsdottir, V and Wuttke, M and Lecoeur, C and Preuss, M and Bielak, LF and Graff, M and Highland, HM and Justice, AE and Liu, DJ and Marouli, E and Peloso, GM and Warren, HR and Afaq, S and Afzal, S and Ahlqvist, E and Almgren, P and Amin, N and Bang, LB and Bertoni, AG and Bombieri, C and Bork-Jensen, J and Brandslund, I and Brody, JA and Burtt, NP and Canouil, M and Chen, Y-DI and Cho, YS and Christensen, C and Eastwood,},
doi = {10.1038/s41588-018-0084-1},
journal = {Nature Genetics},
pages = {559--559},
title = {Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes},
url = {http://dx.doi.org/10.1038/s41588-018-0084-1},
volume = {50},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
AU - Mahajan,A
AU - Wessel,J
AU - Willems,SM
AU - Zhao,W
AU - Robertson,NR
AU - Chu,AY
AU - Gan,W
AU - Kitajima,H
AU - Taliun,D
AU - Rayner,NW
AU - Guo,X
AU - Lu,Y
AU - Li,M
AU - Jensen,RA
AU - Hu,Y
AU - Huo,S
AU - Lohman,KK
AU - Zhang,W
AU - Cook,JP
AU - Prins,BP
AU - Flannick,J
AU - Grarup,N
AU - Trubetskoy,VV
AU - Kravic,J
AU - Kim,YJ
AU - Rybin,DV
AU - Yaghootkar,H
AU - Mueller-Nurasyid,M
AU - Meidtner,K
AU - Li-Gao,R
AU - Varga,TV
AU - Marten,J
AU - Li,J
AU - Smith,AV
AU - An,P
AU - Ligthart,S
AU - Gustafsson,S
AU - Malerba,G
AU - Demirkan,A
AU - Tajes,JF
AU - Steinthorsdottir,V
AU - Wuttke,M
AU - Lecoeur,C
AU - Preuss,M
AU - Bielak,LF
AU - Graff,M
AU - Highland,HM
AU - Justice,AE
AU - Liu,DJ
AU - Marouli,E
AU - Peloso,GM
AU - Warren,HR
AU - Afaq,S
AU - Afzal,S
AU - Ahlqvist,E
AU - Almgren,P
AU - Amin,N
AU - Bang,LB
AU - Bertoni,AG
AU - Bombieri,C
AU - Bork-Jensen,J
AU - Brandslund,I
AU - Brody,JA
AU - Burtt,NP
AU - Canouil,M
AU - Chen,Y-DI
AU - Cho,YS
AU - Christensen,C
AU - Eastwood,SV
AU - Eckardt,K-U
AU - Fischer,K
AU - Gambaro,G
AU - Giedraitis,V
AU - Grove,ML
AU - de,Haan HG
AU - Hackinger,S
AU - Hai,Y
AU - Han,S
AU - Tybjaerg-Hansen,A
AU - Hivert,M-F
AU - Isomaa,B
AU - Jager,S
AU - Jorgensen,ME
AU - Jorgensen,T
AU - Karajamaki,A
AU - Kim,B-J
AU - Kim,SS
AU - Koistinen,HA
AU - Kovacs,P
AU - Kriebel,J
AU - Kronenberg,F
AU - Lall,K
AU - Lange,LA
AU - Lee,J-J
AU - Lehne,B
AU - Li,H
AU - Lin,K-H
AU - Linneberg,A
AU - Liu,C-T
AU - Liu,J
AU - Loh,M
AU - Magi,R
AU - Mamakou,V
AU - McKean-Cowdin,R
AU - Nadkarni,G
AU - Neville,M
AU - Nielsen,SF
AU - Ntalla,I
AU - Peyser,PA
AU - Rathmann,W
AU - Rice,K
AU - Rich,SS
AU - Rode,L
AU - Rolandsson,O
AU - Schonherr,S
AU - Selvin,E
AU - Small,KS
AU - Stancakova,A
AU - Surendran,P
AU - Taylor,KD
AU - Teslovich,TM
AU - Thorand,B
AU - Thorleifsson,G
AU - Tin,A
AU - Tonjes,A
AU - Varbo,A
AU - Witte,DR
AU - Wood,AR
AU - Yajnik,P
AU - Yao,J
AU - Yengo,L
AU - Young,R
AU - Amouyel,P
AU - Boeing,H
AU - Boerwinkle,E
AU - Bottinger,EP
AU - Chowdhury,R
AU - Collins,FS
AU - Dedoussis,G
AU - Dehghan,A
AU - Deloukas,P
AU - Ferrario,MM
AU - Ferrieres,J
AU - Florez,JC
AU - Frossard,P
AU - Gudnason,V
AU - Harris,TB
AU - Heckbert,SR
AU - Howson,JMM
AU - Ingelsson,M
AU - Kathiresan,S
AU - Kee,F
AU - Kuusisto,J
AU - Langenberg,C
AU - Launer,LJ
AU - Lindgren,CM
AU - Mannisto,S
AU - Meitinger,T
AU - Melander,O
AU - Mohlke,KL
AU - Moitry,M
AU - Morris,AD
AU - Murray,AD
AU - de,Mutsert R
AU - Orho-Melander,M
AU - Owen,KR
AU - Perola,M
AU - Peters,A
AU - Province,MA
AU - Rasheed,A
AU - Ridker,PM
AU - Rivadineira,F
AU - Rosendaal,FR
AU - Rosengren,AH
AU - Salomaa,V
AU - Sheu,WH-H
AU - Sladek,R
AU - Smith,BH
AU - Strauch,K
AU - Uitterlinden,AG
AU - Varma,R
AU - Wil
DO - 10.1038/s41588-018-0084-1
EP - 559
PY - 2018///
SN - 1061-4036
SP - 559
TI - Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
T2 - Nature Genetics
UR - http://dx.doi.org/10.1038/s41588-018-0084-1
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000429529300016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.nature.com/articles/s41588-018-0084-1
UR - http://hdl.handle.net/10044/1/72114
VL - 50
ER -