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IRIS
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.
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis / Stavroula, Kanoni; Sarah E, Graham; Yuxuan, Wang; Ida, Surakka; Shweta, Ramdas; Xiang, Zhu; Shoa L, Clarke; Konain Fatima, Bhatti; Sailaja, Vedantam; Thomas W, Winkler; Adam E, Locke; Eirini, Marouli; Greg J M, Zajac; Kuan-Han H, Wu; Ioanna, Ntalla; Qin, Hui; Derek, Klarin; Austin T, Hilliard; Zeyuan, Wang; Chao, Xue; Gudmar, Thorleifsson; Anna, Helgadottir; Daniel F, Gudbjartsson; Hilma, Holm; Isleifur, Olafsson; Mi Yeong, Hwang; Sohee, Han; Masato, Akiyama; Saori, Sakaue; Chikashi, Terao; Masahiro, Kanai; Wei, Zhou; Ben M, Brumpton; Humaira, Rasheed; Aki S, Havulinna; Yogasudha, Veturi; Jennifer Allen, Pacheco; Elisabeth A, Rosenthal; Todd, Lingren; Qiping, Feng; Iftikhar J, Kullo; Akira, Narita; Jun, Takayama; Hilary C, Martin; Karen A, Hunt; Bhavi, Trivedi; Jeffrey, Haessler; Franco, Giulianini; Yuki, Bradford; Jason E, Miller; Archie, Campbell; Kuang, Lin; Iona Y, Millwood; Asif, Rasheed; George, Hindy; Jessica D, Faul; Wei, Zhao; David R, Weir; Constance, Turman; Hongyan, Huang; Mariaelisa, Graff; Ananyo, Choudhury; Dhriti, Sengupta; Anubha, Mahajan; Michael R, Brown; Weihua, Zhang; Ketian, Yu; Ellen M, Schmidt; Anita, Pandit; Stefan, Gustafsson; Xianyong, Yin; Jian'An, Luan; Jing-Hua, Zhao; Fumihiko, Matsuda; Hye-Mi, Jang; Kyungheon, Yoon; Carolina, Medina-Gomez; Achilleas, Pitsillides; Jouke Jan, Hottenga; Andrew R, Wood; Yingji, Ji; Zishan, Gao; Simon, Haworth; Noha A, Yousri; Ruth E, Mitchell; Jin Fang, Chai; Mette, Aadahl; Anne A, Bjerregaard; Jie, Yao; Ani, Manichaikul; Chii-Min, Hwu; Yi-Jen, Hung; Helen R, Warren; Julia, Ramirez; Jette, Bork-Jensen; Line L, Kårhus; Anuj, Goel; Maria, Sabater-Lleal; Raymond, Noordam; Pala, Mauro; Floris, Matteo; Aaron F, Mcdaid; Pedro, Marques-Vidal; Matthias, Wielscher; Stella, Trompet; Naveed, Sattar; Line T, Møllehave; Matthias, Munz; Lingyao, Zeng; Jianfeng, Huang; Bin, Yang; Alaitz, Poveda; Azra, Kurbasic; Claudia, Lamina; Lukas, Forer; Markus, Scholz; Tessel E, Galesloot; Jonathan P, Bradfield; Sanni E, Ruotsalainen; Ewarwick, Daw; Joseph M, Zmuda; Jonathan S, Mitchell; Christian, Fuchsberger; Henry, Christensen; Jennifer A, Brody; Miguel, Vazquez-Moreno; Mary F, Feitosa; Mary K, Wojczynski; Zhe, Wang; Michael H, Preuss; Massimo, Mangino; Paraskevi, Christofidou; Niek, Verweij; Jan W, Benjamins; Jorgen, Engmann; Noah L, Tsao; Anurag, Verma; Roderick C, Slieker; Ken Sin, Lo; Nuno R, Zilhao; Phuong, Le; Marcus E, Kleber; Graciela E, Delgado; Shaofeng, Huo; Daisuke D, Ikeda; Hiroyuki, Iha; Jian, Yang; Jun, Liu; Ayşe, Demirkan; Hampton L, Leonard; Jonathan, Marten; Mirjam, Frank; Börge, Schmidt; Laura J, Smyth; Marisa, Cañadas-Garre; Chaolong, Wang; Masahiro, Nakatochi; Andrew, Wong; Nina, Hutri-Kähönen; Xueling, Sim; Rui, Xia; Alicia, Huerta-Chagoya; Juan Carlos, Fernandez-Lopez; Valeriya, Lyssenko; Suraj S, Nongmaithem; Swati, Bayyana; Heather M, Stringham; Marguerite R, Irvin; Christopher, Oldmeadow; Han-Na, Kim; Seungho, Ryu; Paul R H J, Timmers; Liubov, Arbeeva; Rajkumar, Dorajoo; Leslie A, Lange; Gauri, Prasad; Laura, Lorés-Motta; Marc, Pauper; Jirong, Long; Xiaohui, Li; Elizabeth, Theusch; Fumihiko, Takeuchi; Cassandra N, Spracklen; Anu, Loukola; Sailalitha, Bollepalli; Sophie C, Warner; Ya Xing, Wang; Wen B, Wei; Teresa, Nutile; Daniela, Ruggiero; Yun Ju, Sung; Shufeng, Chen; Fangchao, Liu; Jingyun, Yang; Katherine A, Kentistou; Bernhard, Banas; Giuseppe Giovanni, Nardone; Karina, Meidtner; Lawrence F, Bielak; Jennifer A, Smith; Prashantha, Hebbar; Aliki-Eleni, Farmaki; Edith, Hofer; Maoxuan, Lin; Maria Pina, Concas; Simona, Vaccargiu; Peter J, van der Most; Niina, Pitkänen; Brian E, Cade; Sander W, van der Laan; Kumaraswamy Naidu, Chitrala; Stefan, Weiss; Amy R, Bentley; Ayo P, Doumatey; Adebowale A, Adeyemo; Jong Young, Lee; Eva R B, Petersen; Aneta A, Nielsen; Hyeok Sun, Choi; Maria, Nethander; Sandra, Freitag-Wolf; Lorraine, Southam; Nigel W, Rayner; Carol A, Wang; Shih-Yi, Lin; Jun-Sing, Wang; Christian, Couture; Leo-Pekka, Lyytikäinen; Kjell, Nikus; Gabriel, Cuellar-Partida; Henrik, Vestergaard; Bertha, Hidalgo; Olga, Giannakopoulou; Qiuyin, Cai; Morgan O, Obura; Jessica, van Setten; Xiaoyin, Li; Jingjing, Liang; Hua, Tang; Natalie, Terzikhan; Jae Hun, Shin; Rebecca D, Jackson; Alexander P, Reiner; Lisa Warsinger, Martin; Zhengming, Chen; Liming, Li; Takahisa, Kawaguchi; Joachim, Thiery; Joshua C, Bis; Lenore J, Launer; Huaixing, Li; Mike A, Nalls; Olli T, Raitakari; Sahoko, Ichihara; Sarah H, Wild; Christopher P, Nelson; Harry, Campbell; Susanne, Jäger; Toru, Nabika; Fahd, Al-Mulla; Harri, Niinikoski; Peter S, Braund; Ivana, Kolcic; Peter, Kovacs; Tota, Giardoglou; Tomohiro, Katsuya; Dominique, de Kleijn; Gert J, de Borst; Eung Kweon, Kim; Hieab H H, Adams; M Arfan, Ikram; Xiaofeng, Zhu; Folkert W, Asselbergs; Adriaan O, Kraaijeveld; Joline W J, Beulens; Xiao-Ou, Shu; Loukianos S, Rallidis; Oluf, Pedersen; Torben, Hansen; Paul, Mitchell; Alex W, Hewitt; Mika, Kähönen; Louis, Pérusse; Claude, Bouchard; Anke, Tönjes; Yii-Der Ida, Chen; Craig E, Pennell; Trevor A, Mori; Wolfgang, Lieb; Andre, Franke; Claes, Ohlsson; Dan, Mellström; Yoon Shin, Cho; Hyejin, Lee; Jian-Min, Yuan; Woon-Puay, Koh; Sang Youl, Rhee; Jeong-Taek, Woo; Iris M, Heid; Klaus J, Stark; Martina E, Zimmermann; Henry, Völzke; Georg, Homuth; Michele K, Evans; Alan B, Zonderman; Ozren, Polasek; Gerard, Pasterkamp; Imo E, Hoefer; Susan, Redline; Katja, Pahkala; Albertine J, Oldehinkel; Harold, Snieder; Ginevra, Biino; Reinhold, Schmidt; Helena, Schmidt; Stefania, Bandinelli; George, Dedoussis; Thangavel Alphonse, Thanaraj; Sharon L R, Kardia; Patricia A, Peyser; Norihiro, Kato; Matthias B, Schulze; Giorgia, Girotto; Carsten A, Böger; Bettina, Jung; Peter K, Joshi; David A, Bennett; Philip L, De Jager; Xiangfeng, Lu; Vasiliki, Mamakou; Morris, Brown; Mark J, Caulfield; Patricia B, Munroe; Xiuqing, Guo; Marina, Ciullo; Jost B, Jonas; Nilesh J, Samani; Jaakko, Kaprio; Päivi, Pajukanta; Teresa, Tusié-Luna; Carlos A, Aguilar-Salinas; Linda S, Adair; Sonny Augustin, Bechayda; H Janaka, de Silva; Ananda R, Wickremasinghe; Ronald M, Krauss; Jer-Yuarn, Wu; Wei, Zheng; Anneke Iden, Hollander; Dwaipayan, Bharadwaj; Adolfo, Correa; James G, Wilson; Lars, Lind; Chew-Kiat, Heng; Amanda E, Nelson; Yvonne M, Golightly; James F, Wilson; Brenda, Penninx; Hyung-Lae, Kim; John, Attia; Rodney J, Scott; D C, Rao; Donna K, Arnett; Steven C, Hunt; Mark, Walker; Heikki A, Koistinen; Giriraj R, Chandak; Josep M, Mercader; Maria C, Costanzo; Dongkeun, Jang; Noël P, Burtt; Clicerio Gonzalez, Villalpando; Lorena, Orozco; Myriam, Fornage; Eshyong, Tai; Rob M, van Dam; Terho, Lehtimäki; Nish, Chaturvedi; Mitsuhiro, Yokota; Jianjun, Liu; Dermot F, Reilly; Amy Jayne, Mcknight; Frank, Kee; Karl-Heinz, Jöckel; Mark I, Mccarthy; Colin N A, Palmer; Veronique, Vitart; Caroline, Hayward; Eleanor, Simonsick; Cornelia M, van Duijn; Zi-Bing, Jin; Jia, Qu; Haretsugu, Hishigaki; Xu, Lin; Winfried, März; Vilmundur, Gudnason; Jean-Claude, Tardif; Guillaume, Lettre; Leen M 't, Hart; Petra J M, Elders; Scott M, Damrauer; Meena, Kumari; Mika, Kivimaki; Pim, van der Harst; Tim D, Spector; Ruth J F, Loos; Michael A, Province; Esteban J, Parra; Miguel, Cruz; Bruce M, Psaty; Ivan, Brandslund; Peter P, Pramstaller; Charles N, Rotimi; Kaare, Christensen; Samuli, Ripatti; Elisabeth, Widén; Hakon, Hakonarson; Struan F A, Grant; Lambertus A L M, Kiemeney; Jacqueline, de Graaf; Markus, Loeffler; Florian, Kronenberg; Dongfeng, Gu; Jeanette, Erdmann; Heribert, Schunkert; Paul W, Franks; Allan, Linneberg; J Wouter, Jukema; Amit V, Khera; Minna, Männikkö; Marjo-Riitta, Jarvelin; Zoltan, Kutalik; Cucca, Francesco; Dennis O, Mook-Kanamori; Ko Willems, van Dijk; Hugh, Watkins; David P, Strachan; Niels, Grarup; Peter, Sever; Neil, Poulter; Lee-Ming, Chuang; Jerome I, Rotter; Thomas M, Dantoft; Fredrik, Karpe; Matt J, Neville; Nicholas J, Timpson; Ching-Yu, Cheng; Tien-Yin, Wong; Chiea Chuen, Khor; Hengtong, Li; Charumathi, Sabanayagam; Annette, Peters; Christian, Gieger; Andrew T, Hattersley; Nancy L, Pedersen; Patrik K E, Magnusson; Dorret I, Boomsma; Allegonda H M, Willemsen; Ladrienne, Cupples; Joyce B J, van Meurs; Mohsen, Ghanbari; Penny, Gordon-Larsen; Wei, Huang; Young Jin, Kim; Yasuharu, Tabara; Nicholas J, Wareham; Claudia, Langenberg; Eleftheria, Zeggini; Johanna, Kuusisto; Markku, Laakso; Erik, Ingelsson; Goncalo, Abecasis; John C, Chambers; Jaspal S, Kooner; Paul S, de Vries; Alanna C, Morrison; Scott, Hazelhurst; Michèle, Ramsay; Kari E, North; Martha, Daviglus; Peter, Kraft; Nicholas G, Martin; John B, Whitfield; Shahid, Abbas; Danish, Saleheen; Robin G, Walters; Michael V, Holmes; Corri, Black; Blair H, Smith; Aris, Baras; Anne E, Justice; Julie E, Buring; Paul M, Ridker; Daniel I, Chasman; Charles, Kooperberg; Gen, Tamiya; Masayuki, Yamamoto; David A, van Heel; Richard C, Trembath; Wei-Qi, Wei; Gail P, Jarvik; Bahram, Namjou; M Geoffrey, Hayes; Marylyn D, Ritchie; Pekka, Jousilahti; Veikko, Salomaa; Kristian, Hveem; Bjørn Olav, Åsvold; Michiaki, Kubo; Yoichiro, Kamatani; Yukinori, Okada; Yoshinori, Murakami; Bong-Jo, Kim; Unnur, Thorsteinsdottir; Kari, Stefansson; Jifeng, Zhang; Yeugene, Chen; Yuk-Lam, Ho; Julie A, Lynch; Daniel J, Rader; Philip S, Tsao; Kyong-Mi, Chang; Kelly, Cho; Christopher J, O'Donnell; John M, Gaziano; Peter W F, Wilson; Timothy M, Frayling; Joel N, Hirschhorn; Sekar, Kathiresan; Karen L, Mohlke; Yan V, Sun; Andrew P, Morris; Michael, Boehnke; Christopher D, Brown; Pradeep, Natarajan; Panos, Deloukas; Cristen J, Willer; Themistocles L, Assimes; Gina M, Peloso. - In: GENOME BIOLOGY. - ISSN 1474-760X. - 23:1(2022), p. 268. [10.1186/s13059-022-02837-1]
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Kanoni, Stavroula;Graham, Sarah E;Wang, Yuxuan;Surakka, Ida;Ramdas, Shweta;Zhu, Xiang;Clarke, Shoa L;Bhatti, Konain Fatima;Vedantam, Sailaja;Winkler, Thomas W;Locke, Adam E;Marouli, Eirini;Zajac, Greg J M;Wu, Kuan-Han H;Ntalla, Ioanna;Hui, Qin;Klarin, Derek;Hilliard, Austin T;Wang, Zeyuan;Xue, Chao;Thorleifsson, Gudmar;Helgadottir, Anna;Gudbjartsson, Daniel F;Holm, Hilma;Olafsson, Isleifur;Hwang, Mi Yeong;Han, Sohee;Akiyama, Masato;Sakaue, Saori;Terao, Chikashi;Kanai, Masahiro;Zhou, Wei;Brumpton, Ben M;Rasheed, Humaira;Havulinna, Aki S;Veturi, Yogasudha;Pacheco, Jennifer Allen;Rosenthal, Elisabeth A;Lingren, Todd;Feng, QiPing;Kullo, Iftikhar J;Narita, Akira;Takayama, Jun;Martin, Hilary C;Hunt, Karen A;Trivedi, Bhavi;Haessler, Jeffrey;Giulianini, Franco;Bradford, Yuki;Miller, Jason E;Campbell, Archie;Lin, Kuang;Millwood, Iona Y;Rasheed, Asif;Hindy, George;Faul, Jessica D;Zhao, Wei;Weir, David R;Turman, Constance;Huang, Hongyan;Graff, Mariaelisa;Choudhury, Ananyo;Sengupta, Dhriti;Mahajan, Anubha;Brown, Michael R;Zhang, Weihua;Yu, Ketian;Schmidt, Ellen M;Pandit, Anita;Gustafsson, Stefan;Yin, Xianyong;Luan, Jian'an;Zhao, Jing-Hua;Matsuda, Fumihiko;Jang, Hye-Mi;Yoon, Kyungheon;Medina-Gomez, Carolina;Pitsillides, Achilleas;Hottenga, Jouke Jan;Wood, Andrew R;Ji, Yingji;Gao, Zishan;Haworth, Simon;Yousri, Noha A;Mitchell, Ruth E;Chai, Jin Fang;Aadahl, Mette;Bjerregaard, Anne A;Yao, Jie;Manichaikul, Ani;Hwu, Chii-Min;Hung, Yi-Jen;Warren, Helen R;Ramirez, Julia;Bork-Jensen, Jette;Kårhus, Line L;Goel, Anuj;Sabater-Lleal, Maria;Noordam, Raymond;Mauro, Pala;Matteo, Floris;McDaid, Aaron F;Marques-Vidal, Pedro;Wielscher, Matthias;Trompet, Stella;Sattar, Naveed;Møllehave, Line T;Munz, Matthias;Zeng, Lingyao;Huang, Jianfeng;Yang, Bin;Poveda, Alaitz;Kurbasic, Azra;Lamina, Claudia;Forer, Lukas;Scholz, Markus;Galesloot, Tessel E;Bradfield, Jonathan P;Ruotsalainen, Sanni E;Daw, EWarwick;Zmuda, Joseph M;Mitchell, Jonathan S;Fuchsberger, Christian;Christensen, Henry;Brody, Jennifer A;Vazquez-Moreno, Miguel;Feitosa, Mary F;Wojczynski, Mary K;Wang, Zhe;Preuss, Michael H;Mangino, Massimo;Christofidou, Paraskevi;Verweij, Niek;Benjamins, Jan W;Engmann, Jorgen;Tsao, Noah L;Verma, Anurag;Slieker, Roderick C;Lo, Ken Sin;Zilhao, Nuno R;Le, Phuong;Kleber, Marcus E;Delgado, Graciela E;Huo, Shaofeng;Ikeda, Daisuke D;Iha, Hiroyuki;Yang, Jian;Liu, Jun;Demirkan, Ayşe;Leonard, Hampton L;Marten, Jonathan;Frank, Mirjam;Schmidt, Börge;Smyth, Laura J;Cañadas-Garre, Marisa;Wang, Chaolong;Nakatochi, Masahiro;Wong, Andrew;Hutri-Kähönen, Nina;Sim, Xueling;Xia, Rui;Huerta-Chagoya, Alicia;Fernandez-Lopez, Juan Carlos;Lyssenko, Valeriya;Nongmaithem, Suraj S;Bayyana, Swati;Stringham, Heather M;Irvin, Marguerite R;Oldmeadow, Christopher;Kim, Han-Na;Ryu, Seungho;Timmers, Paul R H J;Arbeeva, Liubov;Dorajoo, Rajkumar;Lange, Leslie A;Prasad, Gauri;Lorés-Motta, Laura;Pauper, Marc;Long, Jirong;Li, Xiaohui;Theusch, Elizabeth;Takeuchi, Fumihiko;Spracklen, Cassandra N;Loukola, Anu;Bollepalli, Sailalitha;Warner, Sophie C;Wang, Ya Xing;Wei, Wen B;Nutile, Teresa;Ruggiero, Daniela;Sung, Yun Ju;Chen, Shufeng;Liu, Fangchao;Yang, Jingyun;Kentistou, Katherine A;Banas, Bernhard;Nardone, Giuseppe Giovanni;Meidtner, Karina;Bielak, Lawrence F;Smith, Jennifer A;Hebbar, Prashantha;Farmaki, Aliki-Eleni;Hofer, Edith;Lin, Maoxuan;Concas, Maria Pina;Vaccargiu, Simona;van der Most, Peter J;Pitkänen, Niina;Cade, Brian E;van der Laan, Sander W;Chitrala, Kumaraswamy Naidu;Weiss, Stefan;Bentley, Amy R;Doumatey, Ayo P;Adeyemo, Adebowale A;Lee, Jong Young;Petersen, Eva R B;Nielsen, Aneta A;Choi, Hyeok Sun;Nethander, Maria;Freitag-Wolf, Sandra;Southam, Lorraine;Rayner, Nigel W;Wang, Carol A;Lin, Shih-Yi;Wang, Jun-Sing;Couture, Christian;Lyytikäinen, Leo-Pekka;Nikus, Kjell;Cuellar-Partida, Gabriel;Vestergaard, Henrik;Hidalgo, Bertha;Giannakopoulou, Olga;Cai, Qiuyin;Obura, Morgan O;van Setten, Jessica;Li, Xiaoyin;Liang, Jingjing;Tang, Hua;Terzikhan, Natalie;Shin, Jae Hun;Jackson, Rebecca D;Reiner, Alexander P;Martin, Lisa Warsinger;Chen, Zhengming;Li, Liming;Kawaguchi, Takahisa;Thiery, Joachim;Bis, Joshua C;Launer, Lenore J;Li, Huaixing;Nalls, Mike A;Raitakari, Olli T;Ichihara, Sahoko;Wild, Sarah H;Nelson, Christopher P;Campbell, Harry;Jäger, Susanne;Nabika, Toru;Al-Mulla, Fahd;Niinikoski, Harri;Braund, Peter S;Kolcic, Ivana;Kovacs, Peter;Giardoglou, Tota;Katsuya, Tomohiro;de Kleijn, Dominique;de Borst, Gert J;Kim, Eung Kweon;Adams, Hieab H H;Ikram, M Arfan;Zhu, Xiaofeng;Asselbergs, Folkert W;Kraaijeveld, Adriaan O;Beulens, Joline W J;Shu, Xiao-Ou;Rallidis, Loukianos S;Pedersen, Oluf;Hansen, Torben;Mitchell, Paul;Hewitt, Alex W;Kähönen, Mika;Pérusse, Louis;Bouchard, Claude;Tönjes, Anke;Chen, Yii-Der Ida;Pennell, Craig E;Mori, Trevor A;Lieb, Wolfgang;Franke, Andre;Ohlsson, Claes;Mellström, Dan;Cho, Yoon Shin;Lee, Hyejin;Yuan, Jian-Min;Koh, Woon-Puay;Rhee, Sang Youl;Woo, Jeong-Taek;Heid, Iris M;Stark, Klaus J;Zimmermann, Martina E;Völzke, Henry;Homuth, Georg;Evans, Michele K;Zonderman, Alan B;Polasek, Ozren;Pasterkamp, Gerard;Hoefer, Imo E;Redline, Susan;Pahkala, Katja;Oldehinkel, Albertine J;Snieder, Harold;Biino, Ginevra;Schmidt, Reinhold;Schmidt, Helena;Bandinelli, Stefania;Dedoussis, George;Thanaraj, Thangavel Alphonse;Kardia, Sharon L R;Peyser, Patricia A;Kato, Norihiro;Schulze, Matthias B;Girotto, Giorgia;Böger, Carsten A;Jung, Bettina;Joshi, Peter K;Bennett, David A;De Jager, Philip L;Lu, Xiangfeng;Mamakou, Vasiliki;Brown, Morris;Caulfield, Mark J;Munroe, Patricia B;Guo, Xiuqing;Ciullo, Marina;Jonas, Jost B;Samani, Nilesh J;Kaprio, Jaakko;Pajukanta, Päivi;Tusié-Luna, Teresa;Aguilar-Salinas, Carlos A;Adair, Linda S;Bechayda, Sonny Augustin;de Silva, H Janaka;Wickremasinghe, Ananda R;Krauss, Ronald M;Wu, Jer-Yuarn;Zheng, Wei;Hollander, Anneke Iden;Bharadwaj, Dwaipayan;Correa, Adolfo;Wilson, James G;Lind, Lars;Heng, Chew-Kiat;Nelson, Amanda E;Golightly, Yvonne M;Wilson, James F;Penninx, Brenda;Kim, Hyung-Lae;Attia, John;Scott, Rodney J;Rao, D C;Arnett, Donna K;Hunt, Steven C;Walker, Mark;Koistinen, Heikki A;Chandak, Giriraj R;Mercader, Josep M;Costanzo, Maria C;Jang, Dongkeun;Burtt, Noël P;Villalpando, Clicerio Gonzalez;Orozco, Lorena;Fornage, Myriam;Tai, EShyong;van Dam, Rob M;Lehtimäki, Terho;Chaturvedi, Nish;Yokota, Mitsuhiro;Liu, Jianjun;Reilly, Dermot F;McKnight, Amy Jayne;Kee, Frank;Jöckel, Karl-Heinz;McCarthy, Mark I;Palmer, Colin N A;Vitart, Veronique;Hayward, Caroline;Simonsick, Eleanor;van Duijn, Cornelia M;Jin, Zi-Bing;Qu, Jia;Hishigaki, Haretsugu;Lin, Xu;März, Winfried;Gudnason, Vilmundur;Tardif, Jean-Claude;Lettre, Guillaume;Hart, Leen M 't;Elders, Petra J M;Damrauer, Scott M;Kumari, Meena;Kivimaki, Mika;van der Harst, Pim;Spector, Tim D;Loos, Ruth J F;Province, Michael A;Parra, Esteban J;Cruz, Miguel;Psaty, Bruce M;Brandslund, Ivan;Pramstaller, Peter P;Rotimi, Charles N;Christensen, Kaare;Ripatti, Samuli;Widén, Elisabeth;Hakonarson, Hakon;Grant, Struan F A;Kiemeney, Lambertus A L M;de Graaf, Jacqueline;Loeffler, Markus;Kronenberg, Florian;Gu, Dongfeng;Erdmann, Jeanette;Schunkert, Heribert;Franks, Paul W;Linneberg, Allan;Jukema, J Wouter;Khera, Amit V;Männikkö, Minna;Jarvelin, Marjo-Riitta;Kutalik, Zoltan;Francesco, Cucca;Mook-Kanamori, Dennis O;van Dijk, Ko Willems;Watkins, Hugh;Strachan, David P;Grarup, Niels;Sever, Peter;Poulter, Neil;Chuang, Lee-Ming;Rotter, Jerome I;Dantoft, Thomas M;Karpe, Fredrik;Neville, Matt J;Timpson, Nicholas J;Cheng, Ching-Yu;Wong, Tien-Yin;Khor, Chiea Chuen;Li, Hengtong;Sabanayagam, Charumathi;Peters, Annette;Gieger, Christian;Hattersley, Andrew T;Pedersen, Nancy L;Magnusson, Patrik K E;Boomsma, Dorret I;Willemsen, Allegonda H M;Cupples, LAdrienne;van Meurs, Joyce B J;Ghanbari, Mohsen;Gordon-Larsen, Penny;Huang, Wei;Kim, Young Jin;Tabara, Yasuharu;Wareham, Nicholas J;Langenberg, Claudia;Zeggini, Eleftheria;Kuusisto, Johanna;Laakso, Markku;Ingelsson, Erik;Abecasis, Goncalo;Chambers, John C;Kooner, Jaspal S;de Vries, Paul S;Morrison, Alanna C;Hazelhurst, Scott;Ramsay, Michèle;North, Kari E;Daviglus, Martha;Kraft, Peter;Martin, Nicholas G;Whitfield, John B;Abbas, Shahid;Saleheen, Danish;Walters, Robin G;Holmes, Michael V;Black, Corri;Smith, Blair H;Baras, Aris;Justice, Anne E;Buring, Julie E;Ridker, Paul M;Chasman, Daniel I;Kooperberg, Charles;Tamiya, Gen;Yamamoto, Masayuki;van Heel, David A;Trembath, Richard C;Wei, Wei-Qi;Jarvik, Gail P;Namjou, Bahram;Hayes, M Geoffrey;Ritchie, Marylyn D;Jousilahti, Pekka;Salomaa, Veikko;Hveem, Kristian;Åsvold, Bjørn Olav;Kubo, Michiaki;Kamatani, Yoichiro;Okada, Yukinori;Murakami, Yoshinori;Kim, Bong-Jo;Thorsteinsdottir, Unnur;Stefansson, Kari;Zhang, Jifeng;Chen, YEugene;Ho, Yuk-Lam;Lynch, Julie A;Rader, Daniel J;Tsao, Philip S;Chang, Kyong-Mi;Cho, Kelly;O'Donnell, Christopher J;Gaziano, John M;Wilson, Peter W F;Frayling, Timothy M;Hirschhorn, Joel N;Kathiresan, Sekar;Mohlke, Karen L;Sun, Yan V;Morris, Andrew P;Boehnke, Michael;Brown, Christopher D;Natarajan, Pradeep;Deloukas, Panos;Willer, Cristen J;Assimes, Themistocles L;Peloso, Gina M
2022-01-01
Abstract
Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/300544
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.