Imperial College London
Dr Weihua Zhang

DrWeihuaZhang

Faculty of Medicine, School of Public Health

Honorary Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 1612weihua.zhang

 
 
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Location

 

165Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kanoni:2022:10.1186/s13059-022-02837-1,
author = {Kanoni, S and Graham, SE and Wang, Y and Surakka, I and Ramdas, S and Zhu, X and Clarke, SL and Bhatti, KF and Vedantam, S and Winkler, TW and Locke, AE and Marouli, E and Zajac, GJM and Wu, K-HH and Ntalla, I and Hui, Q and Klarin, D and Hilliard, AT and Wang, Z and Xue, C and Thorleifsson, G and Helgadottir, A and Gudbjartsson, DF and Holm, H and Olafsson, I and Hwang, MY and Han, S and Akiyama, M and Sakaue, S and Terao, C and Kanai, M and Zhou, W and Brumpton, BM and Rasheed, H and Havulinna, AS and Veturi, Y and Pacheco, JA and Rosenthal, EA and Lingren, T and Feng, Q and Kullo, IJ and Narita, A and Takayama, J and Martin, HC and Hunt, KA and Trivedi, B and Haessler, J and Giulianini, F and Bradford, Y and Miller, JE and Campbell, A and Lin, K and Millwood, IY and Rasheed, A and Hindy, G and Faul, JD and Zhao, W and Weir, DR and Turman, C and Huang, H and Graf, M and Choudhury, A and Sengupta, D and Mahajan, A and Brown, MR and Zhang, W and Yu, K and Schmidt, EM and Pandit, A and },
doi = {10.1186/s13059-022-02837-1},
journal = {Genome Biology},
title = {Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis},
url = {http://dx.doi.org/10.1186/s13059-022-02837-1},
volume = {23},
year = {2022}
}
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TY  - JOUR
AB  - BackgroundGenetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.ResultsTo expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.ConclusionsTaken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
AU  - Kanoni,S
AU  - Graham,SE
AU  - Wang,Y
AU  - Surakka,I
AU  - Ramdas,S
AU  - Zhu,X
AU  - Clarke,SL
AU  - Bhatti,KF
AU  - Vedantam,S
AU  - Winkler,TW
AU  - Locke,AE
AU  - Marouli,E
AU  - Zajac,GJM
AU  - Wu,K-HH
AU  - Ntalla,I
AU  - Hui,Q
AU  - Klarin,D
AU  - Hilliard,AT
AU  - Wang,Z
AU  - Xue,C
AU  - Thorleifsson,G
AU  - Helgadottir,A
AU  - Gudbjartsson,DF
AU  - Holm,H
AU  - Olafsson,I
AU  - Hwang,MY
AU  - Han,S
AU  - Akiyama,M
AU  - Sakaue,S
AU  - Terao,C
AU  - Kanai,M
AU  - Zhou,W
AU  - Brumpton,BM
AU  - Rasheed,H
AU  - Havulinna,AS
AU  - Veturi,Y
AU  - Pacheco,JA
AU  - Rosenthal,EA
AU  - Lingren,T
AU  - Feng,Q
AU  - Kullo,IJ
AU  - Narita,A
AU  - Takayama,J
AU  - Martin,HC
AU  - Hunt,KA
AU  - Trivedi,B
AU  - Haessler,J
AU  - Giulianini,F
AU  - Bradford,Y
AU  - Miller,JE
AU  - Campbell,A
AU  - Lin,K
AU  - Millwood,IY
AU  - Rasheed,A
AU  - Hindy,G
AU  - Faul,JD
AU  - Zhao,W
AU  - Weir,DR
AU  - Turman,C
AU  - Huang,H
AU  - Graf,M
AU  - Choudhury,A
AU  - Sengupta,D
AU  - Mahajan,A
AU  - Brown,MR
AU  - Zhang,W
AU  - Yu,K
AU  - Schmidt,EM
AU  - Pandit,A
AU  - Gustafsson,S
AU  - Yin,X
AU  - Luan,J
AU  - Zhao,J-H
AU  - Matsuda,F
AU  - Jang,H-M
AU  - Yoon,K
AU  - Medina-Gomez,C
AU  - Pitsillides,A
AU  - Hottenga,JJ
AU  - Wood,AR
AU  - Ji,Y
AU  - Gao,Z
AU  - Haworth,S
AU  - Yousri,NA
AU  - Mitchell,RE
AU  - Chai,JF
AU  - Aadahl,M
AU  - Bjerregaard,AA
AU  - Yao,J
AU  - Manichaikul,A
AU  - Hwu,C-M
AU  - Hung,Y-J
AU  - Warren,HR
AU  - Ramirez,J
AU  - Bork-Jensen,J
AU  - Karhus,LL
AU  - Goel,A
AU  - Sabater-Lleal,M
AU  - Noordam,R
AU  - Mauro,P
AU  - Matteo,F
AU  - McDaid,AF
AU  - Marques-Vidal,P
AU  - Wielscher,M
AU  - Trompet,S
AU  - Sattar,N
AU  - Mollehave,LT
AU  - Munz,M
AU  - Zeng,L
AU  - Huang,J
AU  - Yang,B
AU  - Poveda,A
AU  - Kurbasic,A
AU  - Lamina,C
AU  - Forer,L
AU  - Scholz,M
AU  - Galesloot,TE
AU  - Bradfeld,JP
AU  - Ruotsalainen,SE
AU  - Daw,E
AU  - Zmuda,JM
AU  - Mitchell,JS
AU  - Fuchsberger,C
AU  - Christensen,H
AU  - Brody,JA
AU  - Vazquez-Moreno,M
AU  - Feitosa,MF
AU  - Wojczynski,MK
AU  - Wang,Z
AU  - Preuss,MH
AU  - Mangino,M
AU  - Christofdou,P
AU  - Verweij,N
AU  - Benjamins,JW
AU  - Engmann,J
AU  - Tsao,NL
AU  - Verma,A
AU  - Slieker,RC
AU  - Lo,KS
AU  - Zilhao,NR
AU  - Le,P
AU  - Kleber,ME
AU  - Delgado,GE
AU  - Huo,S
AU  - Ikeda,DD
AU  - Iha,H
AU  - Yang,J
AU  - Liu,J
AU  - Leonard,HL
AU  - Marten,J
AU  - Frank,M
AU  - Schmidt,B
AU  - Smyth,LJ
AU  - Canadas-Garre,M
AU  - Wang,C
AU  - Nakatochi,M
AU  - Wong,A
AU  - Hutri-Kahonen,N
AU  - Sim,X
AU  - Xia,R
AU  - Huerta-Chagoya,A
AU  - Fernandez-Lopez,JC
AU  - Lyssenko,V
AU  - Nongmaithem,SS
AU  - Bayyana,S
AU  - Stringham,HM
AU  - Irvin,MR
AU  - Oldmeadow,C
AU  - Kim,H-N
AU  - Ryu,S
AU  - Timmers,PRHJ
AU  - Arbeeva,L
AU  - Dorajoo,R
AU  - Lange,LA
AU  - Prasad,G
AU  - Lores-Motta,L
AU  - Pauper,M
AU  - Long,J
AU  - Li,X
AU  - Theusch,E
AU  - Takeuchi,F
AU  - Spracklen,CN
AU  - Loukola,A
AU  - Bollepalli
DO  - 10.1186/s13059-022-02837-1
PY  - 2022///
SN  - 1474-7596
TI  - Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
T2  - Genome Biology
UR  - http://dx.doi.org/10.1186/s13059-022-02837-1
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000927879600003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://genomebiology.biomedcentral.com/articles/10.1186/s13059-022-02837-1
UR  - http://hdl.handle.net/10044/1/108049
VL  - 23
ER  -
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