نتائج البحث - "Krauss, R.M."

1

دورية أكاديمية

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

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.

وصف الملف: application/pdf

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

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

View record in BASE

النص الكامل

2

دورية أكاديمية

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

المؤلفون: Ramdas, S., Judd, J., Graham, S.E., Kanoni, S., Wang, Y., Surakka, I., Wenz, B., Clarke, S.L., Chesi, A., Wells, A., 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., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Lee, W.J., Hsiung, C.A., 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., Schönherr, S., Forer, L., Scholz, M., Galesloot, T.E., Bradfield, J.P., Ruotsalainen, S.E., Daw, E.W., Zmuda, J.M., Mitchell, J.S., Fuchsberger, C., Christensen, H., Brody, J.A., Le, P., Feitosa, M.F., Wojczynski, M.K., Hemerich, D., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J.W., Engmann, J., Noah, T.L., Verma, A., Slieker, R.C., Lo, K.S., Zilhao, N.R., Kleber, M.E., Delgado, G.E., Huo, S., Ikeda, D.D., Iha, H., Yang, J., Liu, J., Demirkan, A., Leonard, H.L., Marten, J., Emmel, C., 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., Sankareswaran, A., 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., Morgan, A., 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., He, K.Y., 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., Zhu, X., 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., Ida Chen, Y.D., 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., 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., den 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., Walker, M., Scott, L.J., Koistinen, H.A., Chandak, G.R., Mercader, J.M., Villalpando, C.G., Orozco, L., Fornage, M., Tai, E.S., 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., Lu, F., Hishigaki, H., Lin, X., März, W., Gudnason, V., Tardif, J.C., Lettre, G., T Hart, L.M., Elders, PJM, Rader, D.J., 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, L., 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., Willems van Dijk, K., Watkins, H., Strachan, D.P., Grarup, N., Sever, P., Poulter, N., Huey-Herng Sheu, W., 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., de Geus, EJC, Cupples, L.A., van Meurs, JBJ, Ikram, A., Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y.J., Tabara, Y., Wareham, N.J., Langenberg, C., Zeggini, E., Tuomilehto, J., 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.E., Ho, Y.L., Lynch, J.A., Tsao, P.S., Chang, K.M., Cho, K., O'Donnell, C.J., Gaziano, J.M., Wilson, P., Mohlke, K.L., Frayling, T.M., Hirschhorn, J.N., Kathiresan, S., Boehnke, M., Grant, S., Natarajan, P., Sun, Y.V., Morris, A.P., Deloukas, P., Peloso, G., Assimes, T.L., Willer, C.J., Brown, C.D.

المساهمون: Million Veterans Program, Global Lipids Genetics Consortium

المصدر: American journal of human genetics, vol. 109, no. 8, pp. 1366-1387

مصطلحات موضوعية: Chromatin/genetics, Genome-Wide Association Study, Genomics, Humans, Lipids/genetics, Polymorphism, Single Nucleotide/genetics, complex traits, fine-mapping, functional genomics, lipid biology, post-GWAS, regulatory mechanism, variant prioritization

الوصف: A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35931049; info:eu-repo/semantics/altIdentifier/eissn/1537-6605; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_6A99E077C9D62; https://serval.unil.ch/notice/serval:BIB_6A99E077C9D6Test; urn:issn:0002-9297; https://serval.unil.ch/resource/serval:BIB_6A99E077C9D6.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_6A99E077C9D62Test

الإتاحة: https://doi.org/10.1016/j.ajhg.2022.06.012Test
https://serval.unil.ch/notice/serval:BIB_6A99E077C9D6Test
https://serval.unil.ch/resource/serval:BIB_6A99E077C9D6.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_6A99E077C9D62Test

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النص الكامل

3

دورية أكاديمية

A saturated map of common genetic variants associated with human height.

المؤلفون: Yengo, L., Vedantam, S., Marouli, E., Sidorenko, J., Bartell, E., Sakaue, S., Graff, M., Eliasen, A.U., Jiang, Y., Raghavan, S., Miao, J., Arias, J.D., Graham, S.E., Mukamel, R.E., Spracklen, C.N., Yin, X., Chen, S.H., Ferreira, T., Highland, H.H., Ji, Y., Karaderi, T., Lin, K., Lüll, K., Malden, D.E., Medina-Gomez, C., Machado, M., Moore, A., Rüeger, S., Sim, X., Vrieze, S., Ahluwalia, T.S., Akiyama, M., Allison, M.A., Alvarez, M., Andersen, M.K., Ani, A., Appadurai, V., Arbeeva, L., Bhaskar, S., Bielak, L.F., Bollepalli, S., Bonnycastle, L.L., Bork-Jensen, J., Bradfield, J.P., Bradford, Y., Braund, P.S., Brody, J.A., Burgdorf, K.S., Cade, B.E., Cai, H., Cai, Q., Campbell, A., Cañadas-Garre, M., Catamo, E., Chai, J.F., Chai, X., Chang, L.C., Chang, Y.C., Chen, C.H., Chesi, A., Choi, S.H., Chung, R.H., Cocca, M., Concas, M.P., Couture, C., Cuellar-Partida, G., Danning, R., Daw, E.W., Degenhard, F., Delgado, G.E., Delitala, A., Demirkan, A., Deng, X., Devineni, P., Dietl, A., Dimitriou, M., Dimitrov, L., Dorajoo, R., Ekici, A.B., Engmann, J.E., Fairhurst-Hunter, Z., Farmaki, A.E., Faul, J.D., Fernandez-Lopez, J.C., Forer, L., Francescatto, M., Freitag-Wolf, S., Fuchsberger, C., Galesloot, T.E., Gao, Y., Gao, Z., Geller, F., Giannakopoulou, O., Giulianini, F., Gjesing, A.P., Goel, A., Gordon, S.D., Gorski, M., Grove, J., Guo, X., Gustafsson, S., Haessler, J., Hansen, T.F., Havulinna, A.S., Haworth, S.J., He, J., Heard-Costa, N., Hebbar, P., Hindy, G., Ho, Y.A., Hofer, E., Holliday, E., Horn, K., Hornsby, W.E., Hottenga, J.J., Huang, H., Huang, J., Huerta-Chagoya, A., Huffman, J.E., Hung, Y.J., Huo, S., Hwang, M.Y., Iha, H., Ikeda, D.D., Isono, M., Jackson, A.U., Jäger, S., Jansen, I.E., Johansson, I., Jonas, J.B., Jonsson, A., Jørgensen, T., Kalafati, I.P., Kanai, M., Kanoni, S., Kårhus, L.L., Kasturiratne, A., Katsuya, T., Kawaguchi, T., Kember, R.L., Kentistou, K.A., Kim, H.N., Kim, Y.J., Kleber, M.E., Knol, M.J., Kurbasic, A., Lauzon, M., Le, P., Lea, R., Lee, J.Y., Leonard, H.L., Li, S.A., Li, X., Liang, J., Lin, H., Lin, S.Y., Liu, J., Liu, X., Lo, K.S., Long, J., Lores-Motta, L., Luan, J., Lyssenko, V., Lyytikäinen, L.P., Mahajan, A., Mamakou, V., Mangino, M., Manichaikul, A., Marten, J., Mattheisen, M., Mavarani, L., McDaid, A.F., Meidtner, K., Melendez, T.L., Mercader, J.M., Milaneschi, Y., Miller, J.E., Millwood, I.Y., Mishra, P.P., Mitchell, R.E., Møllehave, L.T., Morgan, A., Mucha, S., Munz, M., Nakatochi, M., Nelson, C.P., Nethander, M., Nho, C.W., Nielsen, A.A., Nolte, I.M., Nongmaithem, S.S., Noordam, R., Ntalla, I., Nutile, T., Pandit, A., Christofidou, P., Pärna, K., Pauper, M., Petersen, ERB, Petersen, L.V., Pitkänen, N., Polašek, O., Poveda, A., Preuss, M.H., Pyarajan, S., Raffield, L.M., Rakugi, H., Ramirez, J., Rasheed, A., Raven, D., Rayner, N.W., Riveros, C., Rohde, R., Ruggiero, D., Ruotsalainen, S.E., Ryan, K.A., Sabater-Lleal, M., Saxena, R., Scholz, M., Sendamarai, A., Shen, B., Shi, J., Shin, J.H., Sidore, C., Sitlani, C.M., Slieker, R.C., Smit, RAJ, Smith, A.V., Smith, J.A., Smyth, L.J., Southam, L., Steinthorsdottir, V., Sun, L., Takeuchi, F., Tallapragada, DSP, Taylor, K.D., Tayo, B.O., Tcheandjieu, C., Terzikhan, N., Tesolin, P., Teumer, A., Theusch, E., Thompson, D.J., Thorleifsson, G., Timmers, PRHJ, Trompet, S., Turman, C., Vaccargiu, S., van der Laan, S.W., van der Most, P.J., van Klinken, J.B., van Setten, J., Verma, S.S., Verweij, N., Veturi, Y., Wang, C.A., Wang, C., Wang, L., Wang, Z., Warren, H.R., Bin Wei, W., Wickremasinghe, A.R., Wielscher, M., Wiggins, K.L., Winsvold, B.S., Wong, A., Wu, Y., Wuttke, M., Xia, R., Xie, T., Yamamoto, K., Yang, J., Yao, J., Young, H., Yousri, N.A., Yu, L., Zeng, L., Zhang, W., Zhang, X., Zhao, J.H., Zhao, W., Zhou, W., Zimmermann, M.E., Zoledziewska, M., Adair, L.S., Adams, HHH, Aguilar-Salinas, C.A., Al-Mulla, F., Arnett, D.K., Asselbergs, F.W., Åsvold, B.O., Attia, J., Banas, B., Bandinelli, S., Bennett, D.A., Bergler, T., Bharadwaj, D., Biino, G., Bisgaard, H., Boerwinkle, E., Böger, C.A., Bønnelykke, K., Boomsma, D.I., Børglum, A.D., Borja, J.B., Bouchard, C., Bowden, D.W., Brandslund, I., Brumpton, B., Buring, J.E., Caulfield, M.J., Chambers, J.C., Chandak, G.R., Chanock, S.J., Chaturvedi, N., Chen, Y.I., Chen, Z., Cheng, C.Y., Christophersen, I.E., Ciullo, M., Cole, J.W., Collins, F.S., Cooper, R.S., Cruz, M., Cucca, F., Cupples, L.A., Cutler, M.J., Damrauer, S.M., Dantoft, T.M., de Borst, G.J., de Groot, LCPGM, De Jager, P.L., de Kleijn, DPV, Janaka de Silva, H., Dedoussis, G.V., den Hollander, A.I., Du, S., Easton, D.F., Elders, PJM, Eliassen, A.H., Ellinor, P.T., Elmståhl, S., Erdmann, J., Evans, M.K., Fatkin, D., Feenstra, B., Feitosa, M.F., Ferrucci, L., Ford, I., Fornage, M., Franke, A., Franks, P.W., Freedman, B.I., Gasparini, P., Gieger, C., Girotto, G., Goddard, M.E., Golightly, Y.M., Gonzalez-Villalpando, C., Gordon-Larsen, P., Grallert, H., Grant, SFA, Grarup, N., Griffiths, L., Gudnason, V., Haiman, C., Hakonarson, H., Hansen, T., Hartman, C.A., Hattersley, A.T., Hayward, C., Heckbert, S.R., Heng, C.K., Hengstenberg, C., Hewitt, A.W., Hishigaki, H., Hoyng, C.B., Huang, P.L., Huang, W., Hunt, S.C., Hveem, K., Hyppönen, E., Iacono, W.G., Ichihara, S., Ikram, M.A., Isasi, C.R., Jackson, R.D., Jarvelin, M.R., Jin, Z.B., Jöckel, K.H., Joshi, P.K., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kang, K.D., Kaprio, J., Kardia, SLR, Karpe, F., Kato, N., Kee, F., Kessler, T., Khera, A.V., Khor, C.C., Kiemeney, LALM, Kim, B.J., Kim, E.K., Kim, H.L., Kirchhof, P., Kivimaki, M., Koh, W.P., Koistinen, H.A., Kolovou, G.D., Kooner, J.S., Kooperberg, C., Köttgen, A., Kovacs, P., Kraaijeveld, A., Kraft, P., Krauss, R.M., Kumari, M., Kutalik, Z., Laakso, M., Lange, L.A., Langenberg, C., Launer, L.J., Le Marchand, L., Lee, H., Lee, N.R., Lehtimäki, T., Li, H., Li, L., Lieb, W., Lin, X., Lind, L., Linneberg, A., Liu, C.T., Loeffler, M., London, B., Lubitz, S.A., Lye, S.J., Mackey, D.A., Mägi, R., Magnusson, PKE, Marcus, G.M., Vidal, P.M., Martin, N.G., März, W., Matsuda, F., McGarrah, R.W., McGue, M., McKnight, A.J., Medland, S.E., Mellström, D., Metspalu, A., Mitchell, B.D., Mitchell, P., Mook-Kanamori, D.O., Morris, A.D., Mucci, L.A., Munroe, P.B., Nalls, M.A., Nazarian, S., Nelson, A.E., Neville, M.J., Newton-Cheh, C., Nielsen, C.S., Nöthen, M.M., Ohlsson, C., Oldehinkel, A.J., Orozco, L., Pahkala, K., Pajukanta, P., Palmer, CNA, Parra, E.J., Pattaro, C., Pedersen, O., Pennell, C.E., Penninx, BWJH, Perusse, L., Peters, A., Peyser, P.A., Porteous, D.J., Posthuma, D., Power, C., Pramstaller, P.P., Province, M.A., Qi, Q., Qu, J., Rader, D.J., Raitakari, O.T., Ralhan, S., Rallidis, L.S., Rao, D.C., Redline, S., Reilly, D.F., Reiner, A.P., Rhee, S.Y., Ridker, P.M., Rienstra, M., Ripatti, S., Ritchie, M.D., Roden, D.M., Rosendaal, F.R., Rotter, J.I., Rudan, I., Rutters, F., Sabanayagam, C., Saleheen, D., Salomaa, V., Samani, N.J., Sanghera, D.K., Sattar, N., Schmidt, B., Schmidt, H., Schmidt, R., Schulze, M.B., Schunkert, H., Scott, L.J., Scott, R.J., Sever, P., Shiroma, E.J., Shoemaker, M.B., Shu, X.O., Simonsick, E.M., Sims, M., Singh, J.R., Singleton, A.B., Sinner, M.F., Smith, J.G., Snieder, H., Spector, T.D., Stampfer, M.J., Stark, K.J., Strachan, D.P., 't Hart, L.M., Tabara, Y., Tang, H., Tardif, J.C., Thanaraj, T.A., Timpson, N.J., Tönjes, A., Tremblay, A., Tuomi, T., Tuomilehto, J., Tusié-Luna, M.T., Uitterlinden, A.G., van Dam, R.M., van der Harst, P., Van der Velde, N., van Duijn, C.M., van Schoor, N.M., Vitart, V., Völker, U., Vollenweider, P., Völzke, H., Wacher-Rodarte, N.H., Walker, M., Wang, Y.X., Wareham, N.J., Watanabe, R.M., Watkins, H., Weir, D.R., Werge, T.M., Widen, E., Wilkens, L.R., Willemsen, G., Willett, W.C., Wilson, J.F., Wong, T.Y., Woo, J.T., Wright, A.F., Wu, J.Y., Xu, H., Yajnik, C.S., Yokota, M., Yuan, J.M., Zeggini, E., Zemel, B.S., Zheng, W., Zhu, X., Zmuda, J.M., Zonderman, A.B., Zwart, J.A., Chasman, D.I., Cho, Y.S., Heid, I.M., McCarthy, M.I., Ng, MCY, O'Donnell, C.J., Rivadeneira, F., Thorsteinsdottir, U., Sun, Y.V., Tai, E.S., Boehnke, M., Deloukas, P., Justice, A.E., Lindgren, C.M., Loos, RJF, Mohlke, K.L., North, K.E., Stefansson, K., Walters, R.G., Winkler, T.W., Young, K.L., Loh, P.R., Esko, T., Assimes, T.L., Auton, A., Abecasis, G.R., Willer, C.J., Locke, A.E., Berndt, S.I., Lettre, G., Frayling, T.M., Okada, Y., Wood, A.R., Visscher, P.M., Hirschhorn, J.N.

المساهمون: 23andMe Research Team, VA Million Veteran Program, DiscovEHR (DiscovEHR and MyCode Community Health Initiative), eMERGE (Electronic Medical Records and Genomics Network), Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, Partida, G.C., Sun, Y., Croteau-Chonka, D., Vonk, J.M., Chanock, S., Le Marchand, L.

المصدر: Nature, vol. 610, no. 7933, pp. 704-712

مصطلحات موضوعية: Humans, Body Height/genetics, Gene Frequency/genetics, Genome, Human/genetics, Genome-Wide Association Study, Haplotypes/genetics, Linkage Disequilibrium/genetics, Polymorphism, Single Nucleotide/genetics, Europe/ethnology, Sample Size, Phenotype, Chromosome Mapping

الوصف: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36224396; info:eu-repo/semantics/altIdentifier/eissn/1476-4687; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_B1664EA457970; https://serval.unil.ch/notice/serval:BIB_B1664EA45797Test; urn:issn:0028-0836; https://serval.unil.ch/resource/serval:BIB_B1664EA45797.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_B1664EA457970Test

الإتاحة: https://doi.org/10.1038/s41586-022-05275-yTest
https://serval.unil.ch/notice/serval:BIB_B1664EA45797Test
https://serval.unil.ch/resource/serval:BIB_B1664EA45797.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_B1664EA457970Test

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4

دورية أكاديمية

The power of genetic diversity in genome-wide association studies of lipids.

المؤلفون: Graham, S.E., Clarke, S.L., Wu, K.H., Kanoni, S., Zajac, GJM, Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Hwang, M.Y., Han, S., Narita, A., Choudhury, A., Bentley, A.R., Ekoru, K., Verma, A., Trivedi, B., Martin, H.C., Hunt, K.A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B.M., Rasheed, H., Ruotsalainen, S.E., Havulinna, A.S., Veturi, Y., Feng, Q., Rosenthal, E.A., Lingren, T., Pacheco, J.A., Pendergrass, S.A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Hindy, G., Rasheed, A., Faul, J.D., Zhao, W., Weir, D.R., Turman, C., Huang, H., Graff, M., 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., Willemsen, G., Wood, A.R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., McDaid, A.F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Møllehave, L.T., Thuesen, B.H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T.E., Bradfield, J.P., Daw, E.W., Zmuda, J.M., Mitchell, J.S., Fuchsberger, C., Christensen, H., Brody, J.A., Feitosa, M.F., Wojczynski, M.K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J.W., Engmann, J., Kember, R.L., 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., Leonard, H.L., Marten, J., Schmidt, B., Arendt, M., 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., Ahmed, M., Jackson, A.U., Irvin, M.R., Oldmeadow, C., Kim, H.N., Ryu, S., Timmers, PRHJ, Arbeeva, L., Dorajoo, R., Lange, L.A., Chai, X., 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., Hung, Y.J., Chen, S., Liu, F., Kentistou, K.A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L.F., Smith, J.A., Hebbar, P., Farmaki, A.E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M.P., Vaccargiu, S., van der Most, P.J., Pitkänen, N., Cade, B.E., Lee, J., van der Laan, S.W., Chitrala, K.N., Weiss, S., Zimmermann, M.E., Lee, J.Y., 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., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M.O., van Setten, J., Schwander, K., Terzikhan, N., Shin, J.H., Jackson, R.D., Reiner, A.P., Martin, L.W., Chen, Z., Li, L., Highland, H.M., Young, K.L., Kawaguchi, T., Thiery, J., Bis, J.C., Nadkarni, G.N., 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., Bhatti, K.F., 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., 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., Chen, Y.E., Bandinelli, S., Dedoussis, G., Thanaraj, T.A., Kardia, SLR, Kato, N., Schulze, M.B., Girotto, G., Jung, B., Böger, C.A., 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., Adair, L.S., Bechayda, S.A., de Silva, H.J., Wickremasinghe, A.R., Krauss, R.M., Wu, J.Y., Zheng, W., den 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., Walker, M., Koistinen, H.A., Chandak, G.R., Yajnik, C.S., Mercader, J.M., Tusié-Luna, T., Aguilar-Salinas, C.A., Villalpando, C.G., Orozco, L., Fornage, M., Tai, E.S., 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., Lu, F., Qu, J., Hishigaki, H., Lin, X., März, W., Parra, E.J., Cruz, M., Gudnason, V., Tardif, J.C., Lettre, G., 't Hart, L.M., Elders, PJM, Damrauer, S.M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T.D., Loos, RJF, Province, M.A., Psaty, B.M., Brandslund, I., Pramstaller, P.P., 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., Cucca, F., Mook-Kanamori, D.O., van Dijk, K.W., Watkins, H., Strachan, D.P., Grarup, N., Sever, P., Poulter, N., 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., de Geus, EJC, Cupples, L.A., 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., 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., Justice, A.E., Baras, A., Buring, J.E., Ridker, P.M., Chasman, D.I., Kooperberg, 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., Thorsteinsdottir, U., Stefansson, K., 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, P., Rotimi, C.N., Hazelhurst, S., Ramsay, M., Trembath, R.C., van Heel, D.A., Tamiya, G., Yamamoto, M., Kim, B.J., Mohlke, K.L., Frayling, T.M., Hirschhorn, J.N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G.M., Brown, C.D., Morris, A.P., Assimes, T.L., Deloukas, P., Sun, Y.V., Willer, C.J.

المساهمون: VA Million Veteran Program, Global Lipids Genetics Consortium*

المصدر: Nature, vol. 600, no. 7890, pp. 675-679

مصطلحات موضوعية: Cardiovascular Diseases/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Humans, Linkage Disequilibrium, Multifactorial Inheritance, Polymorphism, Single Nucleotide/genetics

الوصف: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34887591; info:eu-repo/semantics/altIdentifier/eissn/1476-4687; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E92E8C36729A8; https://serval.unil.ch/notice/serval:BIB_E92E8C36729ATest; urn:issn:0028-0836; https://serval.unil.ch/resource/serval:BIB_E92E8C36729A.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E92E8C36729A8Test

الإتاحة: https://doi.org/10.1038/s41586-021-04064-3Test
https://serval.unil.ch/notice/serval:BIB_E92E8C36729ATest
https://serval.unil.ch/resource/serval:BIB_E92E8C36729A.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E92E8C36729A8Test

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5

دورية أكاديمية

Author Correction: The power of genetic diversity in genome-wide association studies of lipids.

المؤلفون: Graham, S.E., Clarke, S.L., Wu, K.H., Kanoni, S., Zajac, GJM, Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Hwang, M.Y., Han, S., Narita, A., Choudhury, A., Bentley, A.R., Ekoru, K., Verma, A., Trivedi, B., Martin, H.C., Hunt, K.A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B.M., Rasheed, H., Ruotsalainen, S.E., Havulinna, A.S., Veturi, Y., Feng, Q., Rosenthal, E.A., Lingren, T., Pacheco, J.A., Pendergrass, S.A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Hindy, G., Rasheed, A., Faul, J.D., Zhao, W., Weir, D.R., Turman, C., Huang, H., Graff, M., 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., Willemsen, G., Wood, A.R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., McDaid, A.F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Møllehave, L.T., Thuesen, B.H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T.E., Bradfield, J.P., Daw, E.W., Zmuda, J.M., Mitchell, J.S., Fuchsberger, C., Christensen, H., Brody, J.A., Feitosa, M.F., Wojczynski, M.K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J.W., Engmann, J., Kember, R.L., 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., Leonard, H.L., Marten, J., Schmidt, B., Arendt, M., 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., Ahmed, M., Jackson, A.U., Yousri, N.A., Irvin, M.R., Oldmeadow, C., Kim, H.N., Ryu, S., Timmers, PRHJ, Arbeeva, L., Dorajoo, R., Lange, L.A., Chai, X., 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., Hung, Y.J., Chen, S., Liu, F., Kentistou, K.A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L.F., Smith, J.A., Hebbar, P., Farmaki, A.E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M.P., Vaccargiu, S., van der Most, P.J., Pitkänen, N., Cade, B.E., Lee, J., van der Laan, S.W., Chitrala, K.N., Weiss, S., Zimmermann, M.E., Lee, J.Y., 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., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M.O., van Setten, J., Schwander, K., Terzikhan, N., Shin, J.H., Jackson, R.D., Reiner, A.P., Martin, L.W., Chen, Z., Li, L., Highland, H.M., Young, K.L., Kawaguchi, T., Thiery, J., Bis, J.C., Nadkarni, G.N., 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., Bhatti, K.F., 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., 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., Chen, Y.E., Bandinelli, S., Dedoussis, G., Thanaraj, T.A., Kardia, SLR, Kato, N., Schulze, M.B., Girotto, G., Jung, B., Böger, C.A., 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., Adair, L.S., Bechayda, S.A., de Silva, H.J., Wickremasinghe, A.R., Krauss, R.M., Wu, J.Y., Zheng, W., den 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., Yajnik, C.S., Mercader, J.M., Tusié-Luna, T., Aguilar-Salinas, C.A., Villalpando, C.G., Orozco, L., Fornage, M., Tai, E.S., 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., Lu, F., Qu, J., Hishigaki, H., Lin, X., März, W., Parra, E.J., Cruz, M., Gudnason, V., Tardif, J.C., Lettre, G., 't Hart, L.M., Elders, PJM, Damrauer, S.M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T.D., Loos, RJF, Province, M.A., Psaty, B.M., Brandslund, I., Pramstaller, P.P., 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., Cucca, F., Mook-Kanamori, D.O., van Dijk, K.W., Watkins, H., Strachan, D.P., Grarup, N., Sever, P., Poulter, N., 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., de Geus, EJC, Cupples, L.A., 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., 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., Justice, A.E., Baras, A., Buring, J.E., Ridker, P.M., Chasman, D.I., Kooperberg, 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., Thorsteinsdottir, U., Stefansson, K., 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, P., Rotimi, C.N., Hazelhurst, S., Ramsay, M., Trembath, R.C., van Heel, D.A., Tamiya, G., Yamamoto, M., Kim, B.J., Mohlke, K.L., Frayling, T.M., Hirschhorn, J.N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G.M., Brown, C.D., Morris, A.P., Assimes, T.L., Deloukas, P., Sun, Y.V., Willer, C.J.

المساهمون: VA Million Veteran Program, Global Lipids Genetics Consortium, Va Million Veteran Program, Global Lipids Genetics Consortium (ed.)

المصدر: Nature, vol. 618, no. 7965, pp. E19-E20

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37237109; info:eu-repo/semantics/altIdentifier/eissn/1476-4687; https://serval.unil.ch/notice/serval:BIB_ECC86903891ATest; urn:issn:0028-0836

الإتاحة: https://doi.org/10.1038/s41586-023-06194-2Test
https://serval.unil.ch/notice/serval:BIB_ECC86903891ATest

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