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
Rights: cc_by_4
Αριθμός Καταχώρησης: edsbas.10F289F6
Βάση Δεδομένων: BASE