• English
    • العربية
  • العربية
  • Login
  • QU
  • QU Library
  •  Home
  • Communities & Collections
View Item 
  •   Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Medicine
  • Medicine Research
  • View Item
  • Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Medicine
  • Medicine Research
  • View Item
  •      
  •  
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

    Thumbnail
    View/Open
    s13059-022-02837-1.pdf (2.132Mb)
    Date
    2022-12-01
    Author
    Kanoni, Stavroula
    Graham, Sarah E.
    Wang, Yuxuan
    Surakka, Ida
    Ramdas, Shweta
    Zhu, Xiang
    Clarke, Shoa L.
    Bhatti, Konain Fatima
    Vedantam, Sailaja
    Winkler, Thomas W.
    Locke, Adam E.
    Marouli, Eirini
    Zajac, Greg J.M.
    Wu, Kuan Han H.
    Ntalla, Ioanna
    Hui, Qin
    Klarin, Derek
    Hilliard, Austin T.
    Wang, Zeyuan
    Xue, Chao
    Thorleifsson, Gudmar
    Helgadottir, Anna
    Gudbjartsson, Daniel F.
    Holm, Hilma
    Olafsson, Isleifur
    Hwang, Mi Yeong
    Han, Sohee
    Akiyama, Masato
    Sakaue, Saori
    Terao, Chikashi
    Kanai, Masahiro
    Zhou, Wei
    Brumpton, Ben M.
    Rasheed, Humaira
    Havulinna, Aki S.
    Veturi, Yogasudha
    Pacheco, Jennifer Allen
    Rosenthal, Elisabeth A.
    Lingren, Todd
    Feng, Qi Ping
    Kullo, Iftikhar J.
    Narita, Akira
    Takayama, Jun
    Martin, Hilary C.
    Hunt, Karen A.
    Trivedi, Bhavi
    Haessler, Jeffrey
    Giulianini, Franco
    Bradford, Yuki
    Miller, Jason E.
    Campbell, Archie
    Lin, Kuang
    Millwood, Iona Y.
    Rasheed, Asif
    Hindy, George
    Faul, Jessica D.
    Zhao, Wei
    Weir, David R.
    Turman, Constance
    Huang, Hongyan
    Graff, Mariaelisa
    Choudhury, Ananyo
    Sengupta, Dhriti
    Mahajan, Anubha
    Brown, Michael R.
    Zhang, Weihua
    Yu, Ketian
    Schmidt, Ellen M.
    Pandit, Anita
    Gustafsson, Stefan
    Yin, Xianyong
    Luan, Jian’an
    Zhao, Jing Hua
    Matsuda, Fumihiko
    Jang, Hye Mi
    Yoon, Kyungheon
    Medina-Gomez, Carolina
    Pitsillides, Achilleas
    Hottenga, Jouke Jan
    Wood, Andrew R.
    Ji, Yingji
    Gao, Zishan
    Haworth, Simon
    Yousri, Noha A.
    Mitchell, Ruth E.
    Chai, Jin Fang
    Aadahl, Mette
    Bjerregaard, Anne A.
    Yao, Jie
    Manichaikul, Ani
    Hwu, Chii Min
    Hung, Yi Jen
    Warren, Helen R.
    Ramirez, Julia
    Bork-Jensen, Jette
    Kårhus, Line L.
    Goel, Anuj
    Sabater-Lleal, Maria
    Noordam, Raymond
    Mauro, Pala
    ...show more authors ...show less authors
    Metadata
    Show full item record
    Abstract
    Background: Genetic 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. Results: To 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. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
    URI
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144774123&origin=inward
    DOI/handle
    http://dx.doi.org/10.1186/s13059-022-02837-1
    http://hdl.handle.net/10576/47316
    Collections
    • Medicine Research [‎1819‎ items ]

    entitlement


    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Home

    Submit your QU affiliated work

    Browse

    All of Digital Hub
      Communities & Collections Publication Date Author Title Subject Type Language Publisher
    This Collection
      Publication Date Author Title Subject Type Language Publisher

    My Account

    Login

    Statistics

    View Usage Statistics

    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Video