Academic Journal

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

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
Συγγραφείς: Kanoni, S, Graham, SE, Wang, Y, Surakka, I, Ramdas, S, Zhu, X, Clarke, SL, Bhatti, KF, Vedantam, S, Winkler, TW, Locke, AE, Marouli, E, Zajac, GJM, Wu, K-HH, Ntalla, I, Hui, Q, Klarin, D, Hilliard, AT, Wang, Z, Xue, C, Thorleifsson, G, Helgadottir, A, Gudbjartsson, DF, Holm, H, Olafsson, I, Hwang, MY, Han, S, Akiyama, M, Sakaue, S, Terao, C, Kanai, M, Zhou, W, Brumpton, BM, Rasheed, H, Havulinna, AS, Veturi, Y, Pacheco, JA, Rosenthal, EA, Lingren, T, Feng, Q, Kullo, IJ, Narita, A, Takayama, J, Martin, HC, Hunt, KA, Trivedi, B, Haessler, J, Giulianini, F, Bradford, Y, Miller, JE, Campbell, A, Lin, K, Millwood, IY, Rasheed, A, Hindy, G, Faul, JD, Zhao, W, Weir, DR, Turman, C, Huang, H, Graff, M, Choudhury, A, Sengupta, D, Mahajan, A, Brown, MR, Zhang, W, Yu, K, Schmidt, EM, Pandit, A, Gustafsson, S, Yin, X, Luan, J, Zhao, J-H, Matsuda, F, Jang, H-M, Yoon, K, Medina-Gomez, C, Pitsillides, A, Hottenga, JJ, Wood, AR, Ji, Y, Gao, Z, Haworth, S, Yousri, NA, Mitchell, RE, Chai, JF, Aadahl, M, Bjerregaard, AA, Yao, J, Manichaikul, A, Hwu, C-M, Hung, Y-J, Warren, HR, Ramirez, J, Bork-Jensen, J, Kårhus, LL, Goel, A, Sabater-Lleal, M, Noordam, R, Mauro, P, Matteo, F, McDaid, AF, Marques-Vidal, P, Wielscher, M, Trompet, S, Sattar, N, Møllehave, LT, Munz, M, Zeng, L, Huang, J, Yang, B, Poveda, A, Kurbasic, A, Lamina, C, Forer, L, Scholz, M, Galesloot, TE, Bradfield, JP, Ruotsalainen, SE, Daw, E, Zmuda, JM, Mitchell, JS, Fuchsberger, C, Christensen, H, Brody, JA, Vazquez-Moreno, M, Feitosa, MF, Wojczynski, MK, Preuss, MH, Mangino, M, Christofidou, P, Verweij, N, Benjamins, JW, Engmann, J, Tsao, NL, Verma, A, Slieker, RC, Lo, KS, Zilhao, NR, Le, P, Kleber, ME, Delgado, GE, Huo, S, Ikeda, DD, Iha, H, Yang, J, Liu, J, Demirkan, A, Leonard, HL, Marten, J, Frank, M, Schmidt, B, Smyth, LJ, Cañadas-Garre, M, Wang, C, Nakatochi, M, Wong, A, Hutri-Kähönen, N, Sim, X, Xia, R, Huerta-Chagoya, A, Fernandez-Lopez, JC, Lyssenko, V, Nongmaithem, SS, Bayyana, S, Stringham, HM, Irvin, MR, Oldmeadow, C, Kim, H-N, Ryu, S, Timmers, PRHJ, Arbeeva, L, Dorajoo, R, Lange, LA, Prasad, G, Lorés-Motta, L, Pauper, M, Long, J, Li, X, Theusch, E, Takeuchi, F, Spracklen, CN, Loukola, A, Bollepalli, S, Warner, SC, Wang, YX, Wei, WB, Nutile, T, Ruggiero, D, Sung, YJ, Chen, S, Liu, F, Kentistou, KA, Banas, B, Nardone, GG, Meidtner, K, Bielak, LF, Smith, JA, Hebbar, P, Farmaki, A-E, Hofer, E, Lin, M, Concas, MP, Vaccargiu, S, van der Most, PJ, Pitkänen, N, Cade, BE, van der Laan, SW, Chitrala, KN, Weiss, S, Bentley, AR, Doumatey, AP, Adeyemo, AA, Lee, JY, Petersen, ERB, Nielsen, AA, Choi, HS, Nethander, M, Freitag-Wolf, S, Southam, L, Rayner, NW, Wang, CA, 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, MO, van Setten, J, Liang, J, Tang, H, Terzikhan, N, Shin, JH, Jackson, RD, Reiner, AP, Martin, LW, Chen, Z, Li, L, Kawaguchi, T, Thiery, J, Bis, JC, Launer, LJ, Li, H, Nalls, MA, Raitakari, OT, Ichihara, S, Wild, SH, Nelson, CP, Campbell, H, Jäger, S, Nabika, T, Al-Mulla, F, Niinikoski, H, Braund, PS, Kolcic, I, Kovacs, P, Giardoglou, T, Katsuya, T, de Kleijn, D, de Borst, GJ, Kim, EK, Adams, HHH, Ikram, MA, Asselbergs, FW, Kraaijeveld, AO, Beulens, JWJ, Shu, X-O, Rallidis, LS, Pedersen, O, Hansen, T, Mitchell, P, Hewitt, AW, Kähönen, M, Pérusse, L, Bouchard, C, Tönjes, A, Chen, Y-DI, Pennell, CE, Mori, TA, Lieb, W, Franke, A, Ohlsson, C, Mellström, D, Cho, YS, Lee, H, Yuan, J-M, Koh, W-P, Rhee, SY, Woo, J-T, Heid, IM, Stark, KJ, Zimmermann, ME, Völzke, H, Homuth, G, Evans, MK, Zonderman, AB, Polasek, O, Pasterkamp, G, Hoefer, IE, Redline, S, Pahkala, K, Oldehinkel, AJ, Snieder, H, Biino, G, Schmidt, R, Schmidt, H, Bandinelli, S, Dedoussis, G, Thanaraj, TA, Kardia, SLR, Peyser, PA, Kato, N, Schulze, MB, Girotto, G, Böger, CA, Jung, B, Joshi, PK, Bennett, DA, De Jager, PL, Lu, X, Mamakou, V, Brown, M, Caulfield, MJ, Munroe, PB, Guo, X, Ciullo, M, Jonas, JB, Samani, NJ, Kaprio, J, Pajukanta, P, Tusié-Luna, T, Aguilar-Salinas, CA, Adair, LS, Bechayda, SA, de Silva, HJ, Wickremasinghe, AR, Krauss, RM, Wu, J-Y, Zheng, W, Hollander, AI, Bharadwaj, D, Correa, A, Wilson, JG, Lind, L, Heng, C-K, Nelson, AE, Golightly, YM, Wilson, JF, Penninx, B, Kim, H-L, Attia, J, Scott, RJ, Rao, DC, Arnett, DK, Hunt, SC, Walker, M, Koistinen, HA, Chandak, GR, Mercader, JM, Costanzo, MC, Jang, D, Burtt, NP, Villalpando, CG, Orozco, L, Fornage, M, Tai, E, van Dam, RM, Lehtimäki, T, Chaturvedi, N, Yokota, M, Reilly, DF, McKnight, AJ, Kee, F, Jöckel, K-H, McCarthy, MI, Palmer, CNA, Vitart, V, Hayward, C, Simonsick, E, van Duijn, CM, Jin, Z-B, Qu, J, Hishigaki, H, Lin, X, März, W, Gudnason, V, Tardif, J-C, Lettre, G, Hart, LMT, Elders, PJM, Damrauer, SM, Kumari, M, Kivimaki, M, van der Harst, P, Spector, TD, Loos, RJF, Province, MA, Parra, EJ, Cruz, M, Psaty, BM, Brandslund, I, Pramstaller, PP, Rotimi, CN, 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, PW, Linneberg, A, Jukema, JW, Khera, AV, Männikkö, M, Jarvelin, M-R, Kutalik, Z, Francesco, C, Mook-Kanamori, DO, van Dijk, KW, Watkins, H, Strachan, DP, Grarup, N, Sever, P, Poulter, N, Chuang, L-M, Rotter, JI, Dantoft, TM, Karpe, F, Neville, MJ, Timpson, NJ, Cheng, C-Y, Wong, T-Y, Khor, CC, Sabanayagam, C, Peters, A, Gieger, C, Hattersley, AT, Pedersen, NL, Magnusson, PKE, Boomsma, DI, Willemsen, AHM, Cupples, L, van Meurs, JBJ, Ghanbari, M, Gordon-Larsen, P, Huang, W, Kim, YJ, Tabara, Y, Wareham, NJ, Langenberg, C, Zeggini, E, Kuusisto, J, Laakso, M, Ingelsson, E, Abecasis, G, Chambers, JC, Kooner, JS, de Vries, PS, Morrison, AC, Hazelhurst, S, Ramsay, M, North, KE, Daviglus, M, Kraft, P, Martin, NG, Whitfield, JB, Abbas, S, Saleheen, D, Walters, RG, Holmes, MV, Black, C, Smith, BH, Baras, A, Justice, AE, Buring, JE, Ridker, PM, Chasman, DI, Kooperberg, C, Tamiya, G, Yamamoto, M, van Heel, DA, Trembath, RC, Wei, W-Q, Jarvik, GP, Namjou, B, Hayes, MG, Ritchie, MD, Jousilahti, P, Salomaa, V, Hveem, K, Åsvold, BO, Kubo, M, Kamatani, Y, Okada, Y, Murakami, Y, Kim, B-J, Thorsteinsdottir, U, Stefansson, K, Zhang, J, Chen, Y, Ho, Y-L, Lynch, JA, Rader, DJ, Tsao, PS, Chang, K-M, Cho, K, O'Donnell, CJ, Gaziano, JM, Wilson, PWF, Frayling, TM, Hirschhorn, JN, Kathiresan, S, Mohlke, KL, Sun, YV, Morris, AP, Boehnke, M, Brown, CD, Natarajan, P, Deloukas, P, Willer, CJ, Assimes, TL, Peloso, GM
Στοιχεία εκδότη: Springer
Έτος έκδοσης: 2022
Συλλογή: St George's University of London: Repository
Περιγραφή: 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.
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: application/pdf; application/vnd.ms-excel; application/vnd.openxmlformats-officedocument.wordprocessingml.document
Γλώσσα: English
ISSN: 1474-760X
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Kanoni, S; Graham, SE; Wang, Y; Surakka, I; Ramdas, S; Zhu, X; Clarke, SL; Bhatti, KF; Vedantam, S; Winkler, TW; Locke, AE; Marouli, E; Zajac, GJM; Wu, K-HH; Ntalla, I; Hui, Q; Klarin, D; Hilliard, AT; Wang, Z; Xue, C; Thorleifsson, G; Helgadottir, A; Gudbjartsson, DF; Holm, H; Olafsson, I; Hwang, MY; Han, S; Akiyama, M; Sakaue, S; Terao, C; Kanai, M; Zhou, W; Brumpton, BM; Rasheed, H; Havulinna, AS; Veturi, Y; Pacheco, JA; Rosenthal, EA; Lingren, T; Feng, Q; Kullo, IJ; Narita, A; Takayama, J; Martin, HC; Hunt, KA; Trivedi, B; Haessler, J; Giulianini, F; Bradford, Y; Miller, JE; Campbell, A; Lin, K; Millwood, IY; Rasheed, A; Hindy, G; Faul, JD; Zhao, W; Weir, DR; Turman, C; Huang, H; Graff, M; Choudhury, A; Sengupta, D; Mahajan, A; Brown, MR; Zhang, W; Yu, K; Schmidt, EM; Pandit, A; Gustafsson, S; Yin, X; Luan, J; Zhao, J-H; Matsuda, F; Jang, H-M; Yoon, K; Medina-Gomez, C; Pitsillides, A; Hottenga, JJ; Wood, AR; Ji, Y; Gao, Z; Haworth, S; Yousri, NA; Mitchell, RE; Chai, JF; Aadahl, M; Bjerregaard, AA; Yao, J; Manichaikul, A; Hwu, C-M; Hung, Y-J; Warren, HR; Ramirez, J; Bork-Jensen, J; Kårhus, LL; Goel, A; Sabater-Lleal, M; Noordam, R; Mauro, P; Matteo, F; McDaid, AF; Marques-Vidal, P; Wielscher, M; Trompet, S; Sattar, N; Møllehave, LT; Munz, M; Zeng, L; Huang, J; Yang, B; Poveda, A; Kurbasic, A; Lamina, C; Forer, L; Scholz, M; Galesloot, TE; Bradfield, JP; Ruotsalainen, SE; Daw, E; Zmuda, JM; Mitchell, JS; Fuchsberger, C; Christensen, H; Brody, JA; Vazquez-Moreno, M; Feitosa, MF; Wojczynski, MK; Wang, Z; Preuss, MH; Mangino, M; Christofidou, P; Verweij, N; Benjamins, JW; Engmann, J; Tsao, NL; Verma, A; Slieker, RC; Lo, KS; Zilhao, NR; Le, P; Kleber, ME; Delgado, GE; Huo, S; Ikeda, DD; Iha, H; Yang, J; Liu, J; Demirkan, A; Leonard, HL; Marten, J; Frank, M; Schmidt, B; Smyth, LJ; Cañadas-Garre, M; Wang, C; Nakatochi, M; Wong, A; Hutri-Kähönen, N; Sim, X; Xia, R; Huerta-Chagoya, A; Fernandez-Lopez, JC; Lyssenko, V; Nongmaithem, SS; Bayyana, S; Stringham, HM; Irvin, MR; Oldmeadow, C; Kim, H-N; Ryu, S; Timmers, PRHJ; Arbeeva, L; Dorajoo, R; Lange, LA; Prasad, G; Lorés-Motta, L; Pauper, M; Long, J; Li, X; Theusch, E; Takeuchi, F; Spracklen, CN; Loukola, A; Bollepalli, S; Warner, SC; Wang, YX; Wei, WB; Nutile, T; Ruggiero, D; Sung, YJ; Chen, S; Liu, F; Yang, J; Kentistou, KA; Banas, B; Nardone, GG; Meidtner, K; Bielak, LF; Smith, JA; Hebbar, P; Farmaki, A-E; Hofer, E; Lin, M; Concas, MP; Vaccargiu, S; van der Most, PJ; Pitkänen, N; Cade, BE; van der Laan, SW; Chitrala, KN; Weiss, S; Bentley, AR; Doumatey, AP; Adeyemo, AA; Lee, JY; Petersen, ERB; Nielsen, AA; Choi, HS; Nethander, M; Freitag-Wolf, S; Southam, L; Rayner, NW; Wang, CA; 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, MO; van Setten, J; Li, X; Liang, J; Tang, H; Terzikhan, N; Shin, JH; Jackson, RD; Reiner, AP; Martin, LW; Chen, Z; Li, L; Kawaguchi, T; Thiery, J; Bis, JC; Launer, LJ; Li, H; Nalls, MA; Raitakari, OT; Ichihara, S; Wild, SH; Nelson, CP; Campbell, H; Jäger, S; Nabika, T; Al-Mulla, F; Niinikoski, H; Braund, PS; Kolcic, I; Kovacs, P; Giardoglou, T; Katsuya, T; de Kleijn, D; de Borst, GJ; Kim, EK; Adams, HHH; Ikram, MA; Zhu, X; Asselbergs, FW; Kraaijeveld, AO; Beulens, JWJ; Shu, X-O; Rallidis, LS; Pedersen, O; Hansen, T; Mitchell, P; Hewitt, AW; Kähönen, M; Pérusse, L; Bouchard, C; Tönjes, A; Chen, Y-DI; Pennell, CE; Mori, TA; Lieb, W; Franke, A; Ohlsson, C; Mellström, D; Cho, YS; Lee, H; Yuan, J-M; Koh, W-P; Rhee, SY; Woo, J-T; Heid, IM; Stark, KJ; Zimmermann, ME; Völzke, H; Homuth, G; Evans, MK; Zonderman, AB; Polasek, O; Pasterkamp, G; Hoefer, IE; Redline, S; Pahkala, K; Oldehinkel, AJ; Snieder, H; Biino, G; Schmidt, R; Schmidt, H; Bandinelli, S; Dedoussis, G; Thanaraj, TA; Kardia, SLR; Peyser, PA; Kato, N; Schulze, MB; Girotto, G; Böger, CA; Jung, B; Joshi, PK; Bennett, DA; De Jager, PL; Lu, X; Mamakou, V; Brown, M; Caulfield, MJ; Munroe, PB; Guo, X; Ciullo, M; Jonas, JB; Samani, NJ; Kaprio, J; Pajukanta, P; Tusié-Luna, T; Aguilar-Salinas, CA; Adair, LS; Bechayda, SA; de Silva, HJ; Wickremasinghe, AR; Krauss, RM; Wu, J-Y; Zheng, W; Hollander, AI; Bharadwaj, D; Correa, A; Wilson, JG; Lind, L; Heng, C-K; Nelson, AE; Golightly, YM; Wilson, JF; Penninx, B; Kim, H-L; Attia, J; Scott, RJ; Rao, DC; Arnett, DK; Hunt, SC; Walker, M; Koistinen, HA; Chandak, GR; Mercader, JM; Costanzo, MC; Jang, D; Burtt, NP; Villalpando, CG; Orozco, L; Fornage, M; Tai, E; van Dam, RM; Lehtimäki, T; Chaturvedi, N; Yokota, M; Liu, J; Reilly, DF; McKnight, AJ; Kee, F; Jöckel, K-H; McCarthy, MI; Palmer, CNA; Vitart, V; Hayward, C; Simonsick, E; van Duijn, CM; Jin, Z-B; Qu, J; Hishigaki, H; Lin, X; März, W; Gudnason, V; Tardif, J-C; Lettre, G; Hart, LMT; Elders, PJM; Damrauer, SM; Kumari, M; Kivimaki, M; van der Harst, P; Spector, TD; Loos, RJF; Province, MA; Parra, EJ; Cruz, M; Psaty, BM; Brandslund, I; Pramstaller, PP; Rotimi, CN; 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, PW; Linneberg, A; Jukema, JW; Khera, AV; Männikkö, M; Jarvelin, M-R; Kutalik, Z; Francesco, C; Mook-Kanamori, DO; van Dijk, KW; Watkins, H; Strachan, DP; Grarup, N; Sever, P; Poulter, N; Chuang, L-M; Rotter, JI; Dantoft, TM; Karpe, F; Neville, MJ; Timpson, NJ; Cheng, C-Y; Wong, T-Y; Khor, CC; Li, H; Sabanayagam, C; Peters, A; Gieger, C; Hattersley, AT; Pedersen, NL; Magnusson, PKE; Boomsma, DI; Willemsen, AHM; Cupples, L; van Meurs, JBJ; Ghanbari, M; Gordon-Larsen, P; Huang, W; Kim, YJ; Tabara, Y; Wareham, NJ; Langenberg, C; Zeggini, E; Kuusisto, J; Laakso, M; Ingelsson, E; Abecasis, G; Chambers, JC; Kooner, JS; de Vries, PS; Morrison, AC; Hazelhurst, S; Ramsay, M; North, KE; Daviglus, M; Kraft, P; Martin, NG; Whitfield, JB; Abbas, S; Saleheen, D; Walters, RG; Holmes, MV; Black, C; Smith, BH; Baras, A; Justice, AE; Buring, JE; Ridker, PM; Chasman, DI; Kooperberg, C; Tamiya, G; Yamamoto, M; van Heel, DA; Trembath, RC; Wei, W-Q; Jarvik, GP; Namjou, B; Hayes, MG; Ritchie, MD; Jousilahti, P; Salomaa, V; Hveem, K; Åsvold, BO; Kubo, M; Kamatani, Y; Okada, Y; Murakami, Y; Kim, B-J; Thorsteinsdottir, U; Stefansson, K; Zhang, J; Chen, Y; Ho, Y-L; Lynch, JA; Rader, DJ; Tsao, PS; Chang, K-M; Cho, K; O'Donnell, CJ; Gaziano, JM; Wilson, PWF; Frayling, TM; Hirschhorn, JN; Kathiresan, S; Mohlke, KL; Sun, YV; Morris, AP; Boehnke, M; Brown, CD; Natarajan, P; Deloukas, P; Willer, CJ; Assimes, TL; Peloso, GM (2022) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. Genome Biol, 23 (1). p. 268. ISSN 1474-760X https://doi.org/10.1186/s13059-022-02837-1 SGUL Authors: Strachan, David Peter
DOI: 10.1186/s13059-022-02837-1
Διαθεσιμότητα: https://openaccess.sgul.ac.uk/id/eprint/115047/
https://openaccess.sgul.ac.uk/id/eprint/115047/1/GLGC_Kanoni_LipidsBiology_Manuscript_Accepted_2022Dec04.pdf
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https://doi.org/10.1186/s13059-022-02837-1
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  Data: Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
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H</searchLink><br /><searchLink fieldCode="AR" term="%22Yuan%2C+J-M%22">Yuan, J-M</searchLink><br /><searchLink fieldCode="AR" term="%22Koh%2C+W-P%22">Koh, W-P</searchLink><br /><searchLink fieldCode="AR" term="%22Rhee%2C+SY%22">Rhee, SY</searchLink><br /><searchLink fieldCode="AR" term="%22Woo%2C+J-T%22">Woo, J-T</searchLink><br /><searchLink fieldCode="AR" term="%22Heid%2C+IM%22">Heid, IM</searchLink><br /><searchLink fieldCode="AR" term="%22Stark%2C+KJ%22">Stark, KJ</searchLink><br /><searchLink fieldCode="AR" term="%22Zimmermann%2C+ME%22">Zimmermann, ME</searchLink><br /><searchLink fieldCode="AR" term="%22Völzke%2C+H%22">Völzke, H</searchLink><br /><searchLink fieldCode="AR" term="%22Homuth%2C+G%22">Homuth, G</searchLink><br /><searchLink fieldCode="AR" term="%22Evans%2C+MK%22">Evans, MK</searchLink><br /><searchLink fieldCode="AR" term="%22Zonderman%2C+AB%22">Zonderman, AB</searchLink><br /><searchLink fieldCode="AR" term="%22Polasek%2C+O%22">Polasek, O</searchLink><br 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term="%22Black%2C+C%22">Black, C</searchLink><br /><searchLink fieldCode="AR" term="%22Smith%2C+BH%22">Smith, BH</searchLink><br /><searchLink fieldCode="AR" term="%22Baras%2C+A%22">Baras, A</searchLink><br /><searchLink fieldCode="AR" term="%22Justice%2C+AE%22">Justice, AE</searchLink><br /><searchLink fieldCode="AR" term="%22Buring%2C+JE%22">Buring, JE</searchLink><br /><searchLink fieldCode="AR" term="%22Ridker%2C+PM%22">Ridker, PM</searchLink><br /><searchLink fieldCode="AR" term="%22Chasman%2C+DI%22">Chasman, DI</searchLink><br /><searchLink fieldCode="AR" term="%22Kooperberg%2C+C%22">Kooperberg, C</searchLink><br /><searchLink fieldCode="AR" term="%22Tamiya%2C+G%22">Tamiya, G</searchLink><br /><searchLink fieldCode="AR" term="%22Yamamoto%2C+M%22">Yamamoto, M</searchLink><br /><searchLink fieldCode="AR" term="%22van+Heel%2C+DA%22">van Heel, DA</searchLink><br /><searchLink fieldCode="AR" term="%22Trembath%2C+RC%22">Trembath, RC</searchLink><br /><searchLink fieldCode="AR" term="%22Wei%2C+W-Q%22">Wei, W-Q</searchLink><br /><searchLink fieldCode="AR" term="%22Jarvik%2C+GP%22">Jarvik, GP</searchLink><br /><searchLink fieldCode="AR" term="%22Namjou%2C+B%22">Namjou, B</searchLink><br /><searchLink fieldCode="AR" term="%22Hayes%2C+MG%22">Hayes, MG</searchLink><br /><searchLink fieldCode="AR" term="%22Ritchie%2C+MD%22">Ritchie, MD</searchLink><br /><searchLink fieldCode="AR" term="%22Jousilahti%2C+P%22">Jousilahti, P</searchLink><br /><searchLink fieldCode="AR" term="%22Salomaa%2C+V%22">Salomaa, V</searchLink><br /><searchLink fieldCode="AR" term="%22Hveem%2C+K%22">Hveem, K</searchLink><br /><searchLink fieldCode="AR" term="%22Åsvold%2C+BO%22">Åsvold, BO</searchLink><br /><searchLink fieldCode="AR" term="%22Kubo%2C+M%22">Kubo, M</searchLink><br /><searchLink fieldCode="AR" term="%22Kamatani%2C+Y%22">Kamatani, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Okada%2C+Y%22">Okada, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Murakami%2C+Y%22">Murakami, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+B-J%22">Kim, B-J</searchLink><br /><searchLink fieldCode="AR" term="%22Thorsteinsdottir%2C+U%22">Thorsteinsdottir, U</searchLink><br /><searchLink fieldCode="AR" term="%22Stefansson%2C+K%22">Stefansson, K</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+J%22">Zhang, J</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Y%22">Chen, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Ho%2C+Y-L%22">Ho, Y-L</searchLink><br /><searchLink fieldCode="AR" term="%22Lynch%2C+JA%22">Lynch, JA</searchLink><br /><searchLink fieldCode="AR" term="%22Rader%2C+DJ%22">Rader, DJ</searchLink><br /><searchLink fieldCode="AR" term="%22Tsao%2C+PS%22">Tsao, PS</searchLink><br /><searchLink fieldCode="AR" term="%22Chang%2C+K-M%22">Chang, K-M</searchLink><br /><searchLink fieldCode="AR" term="%22Cho%2C+K%22">Cho, K</searchLink><br /><searchLink fieldCode="AR" term="%22O'Donnell%2C+CJ%22">O'Donnell, CJ</searchLink><br /><searchLink fieldCode="AR" term="%22Gaziano%2C+JM%22">Gaziano, JM</searchLink><br /><searchLink fieldCode="AR" term="%22Wilson%2C+PWF%22">Wilson, PWF</searchLink><br /><searchLink fieldCode="AR" term="%22Frayling%2C+TM%22">Frayling, TM</searchLink><br /><searchLink fieldCode="AR" term="%22Hirschhorn%2C+JN%22">Hirschhorn, JN</searchLink><br /><searchLink fieldCode="AR" term="%22Kathiresan%2C+S%22">Kathiresan, S</searchLink><br /><searchLink fieldCode="AR" term="%22Mohlke%2C+KL%22">Mohlke, KL</searchLink><br /><searchLink fieldCode="AR" term="%22Sun%2C+YV%22">Sun, YV</searchLink><br /><searchLink fieldCode="AR" term="%22Morris%2C+AP%22">Morris, AP</searchLink><br /><searchLink fieldCode="AR" term="%22Boehnke%2C+M%22">Boehnke, M</searchLink><br /><searchLink fieldCode="AR" term="%22Brown%2C+CD%22">Brown, CD</searchLink><br /><searchLink fieldCode="AR" term="%22Natarajan%2C+P%22">Natarajan, P</searchLink><br /><searchLink fieldCode="AR" term="%22Deloukas%2C+P%22">Deloukas, P</searchLink><br /><searchLink fieldCode="AR" term="%22Willer%2C+CJ%22">Willer, CJ</searchLink><br /><searchLink fieldCode="AR" term="%22Assimes%2C+TL%22">Assimes, TL</searchLink><br /><searchLink fieldCode="AR" term="%22Peloso%2C+GM%22">Peloso, GM</searchLink>
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Springer
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2022
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: St George's University of London: Repository
– Name: Abstract
  Label: Description
  Group: Ab
  Data: 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.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article in journal/newspaper
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: application/pdf; application/vnd.ms-excel; application/vnd.openxmlformats-officedocument.wordprocessingml.document
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 1474-760X
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
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Oldmeadow, C; Kim, H-N; Ryu, S; Timmers, PRHJ; Arbeeva, L; Dorajoo, R; Lange, LA; Prasad, G; Lorés-Motta, L; Pauper, M; Long, J; Li, X; Theusch, E; Takeuchi, F; Spracklen, CN; Loukola, A; Bollepalli, S; Warner, SC; Wang, YX; Wei, WB; Nutile, T; Ruggiero, D; Sung, YJ; Chen, S; Liu, F; Yang, J; Kentistou, KA; Banas, B; Nardone, GG; Meidtner, K; Bielak, LF; Smith, JA; Hebbar, P; Farmaki, A-E; Hofer, E; Lin, M; Concas, MP; Vaccargiu, S; van der Most, PJ; Pitkänen, N; Cade, BE; van der Laan, SW; Chitrala, KN; Weiss, S; Bentley, AR; Doumatey, AP; Adeyemo, AA; Lee, JY; Petersen, ERB; Nielsen, AA; Choi, HS; Nethander, M; Freitag-Wolf, S; Southam, L; Rayner, NW; Wang, CA; 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, MO; van Setten, J; Li, X; Liang, J; Tang, H; Terzikhan, N; Shin, JH; Jackson, RD; Reiner, AP; Martin, LW; Chen, Z; Li, L; Kawaguchi, T; Thiery, J; Bis, JC; Launer, LJ; Li, H; Nalls, MA; 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Grant, SFA; Kiemeney, LALM; de Graaf, J; Loeffler, M; Kronenberg, F; Gu, D; Erdmann, J; Schunkert, H; Franks, PW; Linneberg, A; Jukema, JW; Khera, AV; Männikkö, M; Jarvelin, M-R; Kutalik, Z; Francesco, C; Mook-Kanamori, DO; van Dijk, KW; Watkins, H; Strachan, DP; Grarup, N; Sever, P; Poulter, N; Chuang, L-M; Rotter, JI; Dantoft, TM; Karpe, F; Neville, MJ; Timpson, NJ; Cheng, C-Y; Wong, T-Y; Khor, CC; Li, H; Sabanayagam, C; Peters, A; Gieger, C; Hattersley, AT; Pedersen, NL; Magnusson, PKE; Boomsma, DI; Willemsen, AHM; Cupples, L; van Meurs, JBJ; Ghanbari, M; Gordon-Larsen, P; Huang, W; Kim, YJ; Tabara, Y; Wareham, NJ; Langenberg, C; Zeggini, E; Kuusisto, J; Laakso, M; Ingelsson, E; Abecasis, G; Chambers, JC; Kooner, JS; de Vries, PS; Morrison, AC; Hazelhurst, S; Ramsay, M; North, KE; Daviglus, M; Kraft, P; Martin, NG; Whitfield, JB; Abbas, S; Saleheen, D; Walters, RG; Holmes, MV; Black, C; Smith, BH; Baras, A; Justice, AE; Buring, JE; Ridker, PM; Chasman, DI; Kooperberg, C; Tamiya, G; Yamamoto, M; van Heel, DA; Trembath, RC; Wei, W-Q; Jarvik, GP; Namjou, B; Hayes, MG; Ritchie, MD; Jousilahti, P; Salomaa, V; Hveem, K; Åsvold, BO; Kubo, M; Kamatani, Y; Okada, Y; Murakami, Y; Kim, B-J; Thorsteinsdottir, U; Stefansson, K; Zhang, J; Chen, Y; Ho, Y-L; Lynch, JA; Rader, DJ; Tsao, PS; Chang, K-M; Cho, K; O'Donnell, CJ; Gaziano, JM; Wilson, PWF; Frayling, TM; Hirschhorn, JN; Kathiresan, S; Mohlke, KL; Sun, YV; Morris, AP; Boehnke, M; Brown, CD; Natarajan, P; Deloukas, P; Willer, CJ; Assimes, TL; Peloso, GM (2022) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. Genome Biol, 23 (1). p. 268. ISSN 1474-760X https://doi.org/10.1186/s13059-022-02837-1 SGUL Authors: Strachan, David Peter
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              M: 01
              Type: published
              Y: 2022
          Identifiers:
            – Type: issn-print
              Value: 1474760X
            – Type: issn-locals
              Value: edsbas
            – Type: issn-locals
              Value: edsbas.oa
ResultId 1