دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
المؤلفون: Kanoni, S., Graham, S.E., Wang, Y., Surakka, I., Ramdas, S., Zhu, X., Clarke, S.L., Bhatti, K.F., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Zajac, GJM, Wu, K.H., Ntalla, I., Hui, Q., Klarin, D., Hilliard, A.T., Wang, Z., Xue, C., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Hwang, M.Y., Han, S., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B.M., Rasheed, H., Havulinna, A.S., Veturi, Y., Pacheco, J.A., Rosenthal, E.A., Lingren, T., Feng, Q., Kullo, I.J., Narita, A., Takayama, J., Martin, H.C., Hunt, K.A., Trivedi, B., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Rasheed, A., Hindy, G., Faul, J.D., Zhao, W., Weir, D.R., Turman, C., Huang, H., Graff, M., Choudhury, A., Sengupta, D., Mahajan, A., Brown, M.R., Zhang, W., Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Wood, A.R., Ji, Y., Gao, Z., Haworth, S., Yousri, N.A., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Hwu, C.M., Hung, Y.J., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Mauro, P., Matteo, F., McDaid, A.F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Møllehave, L.T., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T.E., Bradfield, J.P., Ruotsalainen, S.E., Daw, E., Zmuda, J.M., Mitchell, J.S., Fuchsberger, C., Christensen, H., Brody, J.A., Vazquez-Moreno, M., Feitosa, M.F., Wojczynski, M.K., Preuss, M.H., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J.W., Engmann, J., Tsao, N.L., Verma, A., Slieker, R.C., Lo, K.S., Zilhao, N.R., Le, P., Kleber, M.E., Delgado, G.E., Huo, S., Ikeda, D.D., Iha, H., Yang, J., Liu, J., Demirkan, A., Leonard, H.L., Marten, J., Frank, M., Schmidt, B., Smyth, L.J., Cañadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kähönen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J.C., Lyssenko, V., Nongmaithem, S.S., Bayyana, S., Stringham, H.M., Irvin, M.R., Oldmeadow, C., Kim, H.N., Ryu, S., Timmers, PRHJ, Arbeeva, L., Dorajoo, R., Lange, L.A., Prasad, G., Lorés-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C.N., Loukola, A., Bollepalli, S., Warner, S.C., Wang, Y.X., Wei, W.B., Nutile, T., Ruggiero, D., Sung, Y.J., Chen, S., Liu, F., Kentistou, K.A., Banas, B., Nardone, G.G., Meidtner, K., Bielak, L.F., Smith, J.A., Hebbar, P., Farmaki, A.E., Hofer, E., Lin, M., Concas, M.P., Vaccargiu, S., van der Most, P.J., Pitkänen, N., Cade, B.E., van der Laan, S.W., Chitrala, K.N., Weiss, S., Bentley, A.R., Doumatey, A.P., Adeyemo, A.A., Lee, J.Y., Petersen, ERB, Nielsen, A.A., Choi, H.S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N.W., Wang, C.A., Lin, S.Y., Wang, J.S., Couture, C., Lyytikäinen, L.P., Nikus, K., Cuellar-Partida, G., Vestergaard, H., Hidalgo, B., Giannakopoulou, O., Cai, Q., Obura, M.O., van Setten, J., Liang, J., Tang, H., Terzikhan, N., Shin, J.H., Jackson, R.D., Reiner, A.P., Martin, L.W., Chen, Z., Li, L., Kawaguchi, T., Thiery, J., Bis, J.C., Launer, L.J., Li, H., Nalls, M.A., Raitakari, O.T., Ichihara, S., Wild, S.H., Nelson, C.P., Campbell, H., Jäger, S., Nabika, T., Al-Mulla, F., Niinikoski, H., Braund, P.S., Kolcic, I., Kovacs, P., Giardoglou, T., Katsuya, T., de Kleijn, D., de Borst, G.J., Kim, E.K., Adams, HHH, Ikram, M.A., Asselbergs, F.W., Kraaijeveld, A.O., Beulens, JWJ, Shu, X.O., Rallidis, L.S., Pedersen, O., Hansen, T., Mitchell, P., Hewitt, A.W., Kähönen, M., Pérusse, L., Bouchard, C., Tönjes, A., Chen, Y.I., Pennell, C.E., Mori, T.A., Lieb, W., Franke, A., Ohlsson, C., Mellström, D., Cho, Y.S., Lee, H., Yuan, J.M., Koh, W.P., Rhee, S.Y., Woo, J.T., Heid, I.M., Stark, K.J., Zimmermann, M.E., Völzke, H., Homuth, G., Evans, M.K., Zonderman, A.B., Polasek, O., Pasterkamp, G., Hoefer, I.E., Redline, S., Pahkala, K., Oldehinkel, A.J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Bandinelli, S., Dedoussis, G., Thanaraj, T.A., Kardia, SLR, Peyser, P.A., Kato, N., Schulze, M.B., Girotto, G., Böger, C.A., Jung, B., Joshi, P.K., Bennett, D.A., De Jager, P.L., Lu, X., Mamakou, V., Brown, M., Caulfield, M.J., Munroe, P.B., Guo, X., Ciullo, M., Jonas, J.B., Samani, N.J., Kaprio, J., Pajukanta, P., Tusié-Luna, T., Aguilar-Salinas, C.A., Adair, L.S., Bechayda, S.A., de Silva, H.J., Wickremasinghe, A.R., Krauss, R.M., Wu, J.Y., Zheng, W., Hollander, A.I., Bharadwaj, D., Correa, A., Wilson, J.G., Lind, L., Heng, C.K., Nelson, A.E., Golightly, Y.M., Wilson, J.F., Penninx, B., Kim, H.L., Attia, J., Scott, R.J., Rao, D.C., Arnett, D.K., Hunt, S.C., Walker, M., Koistinen, H.A., Chandak, G.R., Mercader, J.M., Costanzo, M.C., Jang, D., Burtt, N.P., Villalpando, C.G., Orozco, L., Fornage, M., Tai, E., van Dam, R.M., Lehtimäki, T., Chaturvedi, N., Yokota, M., Reilly, D.F., McKnight, A.J., Kee, F., Jöckel, K.H., McCarthy, M.I., Palmer, CNA, Vitart, V., Hayward, C., Simonsick, E., van Duijn, C.M., Jin, Z.B., Qu, J., Hishigaki, H., Lin, X., März, W., Gudnason, V., Tardif, J.C., Lettre, G., Hart, LM', Elders, PJM, Damrauer, S.M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T.D., Loos, RJF, Province, M.A., Parra, E.J., Cruz, M., Psaty, B.M., Brandslund, I., Pramstaller, P.P., Rotimi, C.N., Christensen, K., Ripatti, S., Widén, E., Hakonarson, H., Grant, SFA, Kiemeney, LALM, de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P.W., Linneberg, A., Jukema, J.W., Khera, A.V., Männikkö, M., Jarvelin, M.R., Kutalik, Z., Francesco, C., Mook-Kanamori, D.O., van Dijk, K.W., Watkins, H., Strachan, D.P., Grarup, N., Sever, P., Poulter, N., Chuang, L.M., Rotter, J.I., Dantoft, T.M., Karpe, F., Neville, M.J., Timpson, N.J., Cheng, C.Y., Wong, T.Y., Khor, C.C., Sabanayagam, C., Peters, A., Gieger, C., Hattersley, A.T., Pedersen, N.L., Magnusson, PKE, Boomsma, D.I., Willemsen, AHM, Cupples, L., van Meurs, JBJ, Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y.J., Tabara, Y., Wareham, N.J., Langenberg, C., Zeggini, E., Kuusisto, J., Laakso, M., Ingelsson, E., Abecasis, G., Chambers, J.C., Kooner, J.S., de Vries, P.S., Morrison, A.C., Hazelhurst, S., Ramsay, M., North, K.E., Daviglus, M., Kraft, P., Martin, N.G., Whitfield, J.B., Abbas, S., Saleheen, D., Walters, R.G., Holmes, M.V., Black, C., Smith, B.H., Baras, A., Justice, A.E., Buring, J.E., Ridker, P.M., Chasman, D.I., Kooperberg, C., Tamiya, G., Yamamoto, M., van Heel, D.A., Trembath, R.C., Wei, W.Q., Jarvik, G.P., Namjou, B., Hayes, M.G., Ritchie, M.D., Jousilahti, P., Salomaa, V., Hveem, K., Åsvold, B.O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Kim, B.J., Thorsteinsdottir, U., Stefansson, K., Zhang, J., Chen, Y., Ho, Y.L., Lynch, J.A., Rader, D.J., Tsao, P.S., Chang, K.M., Cho, K., O'Donnell, C.J., Gaziano, J.M., Wilson, PWF, Frayling, T.M., Hirschhorn, J.N., Kathiresan, S., Mohlke, K.L., Sun, Y.V., Morris, A.P., Boehnke, M., Brown, C.D., Natarajan, P., Deloukas, P., Willer, C.J., Assimes, T.L., Peloso, G.M.
المصدر: Genome biology, vol. 23, no. 1, pp. 268
سنة النشر: 2022
المجموعة: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
مصطلحات موضوعية: Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Sex Characteristics, Phenotype, Lipids/genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Cholesterol, GWAS, Genetics, Lipids
الوصف: 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. 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. Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1474-7596
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36575460; info:eu-repo/semantics/altIdentifier/eissn/1474-760X; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_3CFF377B19810; https://serval.unil.ch/notice/serval:BIB_3CFF377B1981Test; urn:issn:1474-7596; https://serval.unil.ch/resource/serval:BIB_3CFF377B1981.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_3CFF377B19810Test
DOI: 10.1186/s13059-022-02837-1
الإتاحة: https://doi.org/10.1186/s13059-022-02837-1Test
https://serval.unil.ch/notice/serval:BIB_3CFF377B1981Test
https://serval.unil.ch/resource/serval:BIB_3CFF377B1981.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_3CFF377B19810Test
حقوق: info:eu-repo/semantics/openAccess ; CC BY 4.0 ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.EB164826
قاعدة البيانات: BASE
الوصف
تدمد:14747596
DOI:10.1186/s13059-022-02837-1