Browsing by Author "Deng, X."

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Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions.
(School of Hygiene and Public Health of Johns Hopkins University,Baltimore., 2019) de Vries, P. S.; Brown, M. R.; Bentley, A. R.; Sung, Y. J.; Winkler, T. W.; Ntalla, I.; Schwander, K.; Kraja, A. T.; Guo, X.; Franceschini, N.; Cheng, C. Y.; Sim, X.; Vojinovic, D.; Huffman, J. E.; Musani, S. K.; Li, C.; Feitosa, M.F.; Richard, M.A.; Noordam, R.; Aschard, H.; Bartz, T. M.; Bielak, L. F.; Deng, X.; Dorajoo, R.; Lohman, K.K.; Manning, A. K.; Rankinen, T.; Smith, A. V.; Tajuddin, S. M.; Evangelou, E.; Graff, M.; Alver, M.; Boissel, M.; Chai, J. F.; Chen, X.; Divers, J.; Gandin, I.; Gao, C.; Goel, A.; Hagemeijer, Y.; Harris, S. E.; Hartwig, F. P.; He, M.; Horimoto, A. R. V. R.; Hsu, F. C.; Jackson, A. U.; Kasturiratne, A.; Komulainen, P.; Kühnel, B.; Laguzzi, F.; Lee, J. H.; Luan, J.; Lyytikäinen, L. P.; Matoba, N.; Nolte, I. M.; Pietzner, M.; Riaz, M.; Said, M. A.; Scott, R. A.; Sofer, T.; Stancáková, A.; Takeuchi, F.; Tayo, B. O.; van der Most, P. J.; Varga, T. V.; Wang, Y.; Ware, E. B.; Wen, W.; Yanek, L. R.; Zhang, W.; Zhao, J. H.; Afaq, S.; Amin, N.; Amini, M.; Arking, D. E.; Aung, T.; Ballantyne, C.; Boerwinkle, E.; Broeckel, U.; Campbell, A.; Canouil, M.; Charumathi, S.; Chen, Y. I.; Connell, J. M.; de Faire, U.; de Las Fuentes, L.; de Mutsert, R.; de Silva, H.J.; Ding, J.; Dominiczak, A. F.; Duan, Q.; Eaton, C. B.; Eppinga, R.N.; Faul, J. D.; Fisher, V.; Forrester, T.; Franco, O. H.; Friedlander, Y.; Ghanbari, M.; Giulianini, F.; Grabe, H. J.; Grove, M. L.; Gu, C. C.; Harris, T. B.; Heikkinen, S.; Heng, C. K.; Hirata, M.; Hixson, J. E.; Howard, B. V.; Ikram, M. A.; InterAct Consortium; Jr. Jacobs, D. R.; Johnson, C.; Jonas, J. B.; Kammerer, C. M.; Katsuya, T.; Khor, C. C.; Kilpeläinen, T. O.; Koh, W. P.; Koistinen, H. A.; Kolcic, I.; Kooperberg, C.; Krieger, J. E.; Kritchevsky, S. B.; Kubo, M.; Kuusisto, J.; Lakka, T. A.; Langefeld, C. D.; Langenberg, C.; Launer, L. J.; Lehne, B.; Lemaitre, R. N.; Li, Y.; Liang, J.; Liu, J.; Liu, K.; Loh, M.; Louie, T.; Mägi, R.; Manichaikul, A. W.; McKenzie, C. A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; Mohlke, K. L.; Jr. Mosley, T. H.; Nelson, C. P.; Mukamal, K. J.; Nalls, M. A.; Nauck, M.; Sotoodehnia, N.; O'Connell, J. R.; Palmer, N. D.; Pazoki, R.; Pedersen, N. L.; Peters, A.; Peyser, P. A.; Polasek, O.; Poulter, N.; Raffel, L. J.; Raitakari, O. T.; Reiner, A. P.; Rice, T. K.; Rich, S. S.; Robino, A.; Robinson, J. G.; Rose, L. M.; Rudan, I.; Schmidt, C. O.; Schreiner, P. J.; Scott, W. R.; Sever, P.; Shi, Y.; Sidney, S.; Sims, M.; Smith, B. H.; Smith, J. A.; Snieder, H.; Starr, J. M.; Strauch, K.; Tan, N.; Taylor, K. D.; Teo, Y. Y.; Tham, Y. C.; Uitterlinden, A. G.; van Heemst, D.; Vuckovic, D.; Waldenberger, M.; Wang, L.; Wang, Y.; Wang, Z.; Wei, W. B.; Williams, C.; Sr Wilson, G.; Wojczynski, M. K.; Yao, J.; Yu, B.; Yu, C.; Yuan, J. M.; Zhao, W.; Zonderman, A. B.; Becker, D. M.; Boehnke, M.; Bowden, D. W.; Chambers, J. C.; Deary, I. J.; Esko, T.; Farrall, M.; Franks, P. W.; Freedman, B. I.; Froguel, P.; Gasparini, P.; Gieger, C.; Horta, B. L.; Kamatani, Y.; Kato, N.; Kooner, J. S.; Laakso, M.; Leander, K.; Lehtimäki, T.; Lifelines Cohort, Groningen,; The Netherlands (Lifelines Cohort Study); Magnusson, P. K. E.; Penninx, B.; Pereira, A. C.; Rauramaa, R.; Samani, N.J.; Scott, J.; Shu, X. O.; van der Harst, P.; Wagenknecht, L. E.; Wang, Y. X.; Wareham, N. J.; Watkins, H.; Weir, D. R.; Wickremasinghe, A.R.; Zheng, W.; Elliott, P.; North, K. E.; Bouchard, C.; Evans, M. K.; Gudnason, V.; Liu, C. T.; Liu, Y.; Psaty, B. M.; Ridker, P. M.; van Dam, R. M.; Kardia, S. L. R.; Zhu, X.; Rotimi, C. N.; Mook-Kanamori, D. O.; Fornage, M.; Kelly, T. N.; Fox, E. R.; Hayward, C.; van Duijn, C. M.; Tai, E. S.; Wong, T. Y.; Liu, J.; Rotter, J. I.; Gauderman, W. J.; Province, M. A.; Munroe, P. B.; Rice, K.; Chasman, D. I.; Cupples, L. A.; Rao, D. C.; Morrison, A. C.
An individual's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total of 394,584 individuals from five ancestry groups. Genetic main and interaction effects were jointly assessed by a 2 degrees of freedom (DF) test, and a 1 DF test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in Stage 1 and were evaluated in Stage 2, followed by combined analyses of Stage 1 and Stage 2. In the combined analysis of Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2 DF tests, of which 18 were novel. No genome-wide significant associations were found testing the interaction effect alone. The novel loci included several genes (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.
(Nature Publishing Group, 2019) Bentley, A.R.; Chasman, D. I.; Schwander, K.; Ntalla, I.; Kraja, A.T.; Winkler, T.W.; Brown, M. R.; Sung, Y. J.; Lim, E.; Huffman, J.E.; Vojinovic, D.; Sim, X.; Cheng, C.Y.; Lu, Y.; Liu, J.; Guo, X.; Deng, X.; Musani, S.K.; Li, C.; Feitosa, M.F.; Richard, M.A.; Noordam, R.; Baker, J.; Chen, G.; Aschard, H.; Bartz, T.M.; Ding, J.; Dorajoo, R.; Manning, A.K.; Rankinen, T.; Smith, A. V.; Tajuddin, S.M.; Zhao, W.; Graff, M.; Alver, M.; Boissel, M.; Chai, J. F.; Chen, X.; Divers, J.; Evangelou, E.; Gao, C.; Goel, A.; Hagemeijer, Y.; Harris, S. E.; Hartwig, F. P.; He, M.; Horimoto, A.R.V. R.; Hsu, F.C.; Hung, Y. J.; Jackson, A. U.; Kasturiratne, A.; Komulainen, P.; Kühnel, B.; Leander, K.; Lin, K. H.; Luan, J.; Lyytikäinen, L.P.; Matoba, N.; Nolte, I. M.; Pietzner, M.; Prins, B.; Riaz, M.; Robino, A.; Said, M. A.; Schupf, N.; Scott, R. A.; Sofer, T.; Stancáková, A.; Takeuchi, F.; Tayo, B. O.; van der Most, P. J.; Varga, T. V.; Wang, T. D.; Wang, Y.; Ware, E. B.; Wen, W.; Xiang, Y. B.; Yanek, L. R.; Zhang, W.; Zhao, J. H.; Adeyemo, A.; Afaq, S.; Amin, N.; Amini, M.; Arking, D.E.; Arzumanyan, Z.; Aung, T.; Ballantyne, C.; Barr, R. G.; Bielak, L. F.; Boerwinkle, E.; Bottinger, E.P.; Broeckel, U.; Chen, Y. I.; Charumathi, S.; Canouil, M.; Campbell, A.; Cade, B. E.; Brown, M.; Christensen, K.; de Las Fuentes, L.; Connell, J. M.; Concas, M. P.; COGENT-Kidney Consortium; de Silva, H.J.; de Vries, P. S.; Doumatey, A.; Duan, Q.; Eaton, C. B.; Eppinga, R.N.; Faul, J. D.; Floyd, J.S.; Gigante, B.; Gharib, S. A.; Forouhi, N.G.; Ghanbari, M.; Gao, H.; Gandin, I.; Friedlander, Y.; Forrester, T.; Hixson, J. E.; Hirata, M.; Justice, A. E.; Jonas, J. B.; Johnson, C.; Joehanes, R.; Jia, Y.; EPIC-InterAct Consortium; Ikram, M.A.; Katsuya, T.; Khor, C.C.; Kilpeläinen, T.O.; Koh, W. P.; Kolcic, I.; Kooperberg, C.; Krieger, J.E.; Kritchevsky, S.B.; Kubo, M.; Kuusisto, J.; Lakka, T. A.; Langefeld, C.D.; Langenberg, C.; Launer, L. J.; Lehne, B.; Lewis, C. E.; Li, Y.; Liang, J.; Lin, S.; Liu, C.T.; Liu, J.; Liu, K.; Loh, M.; Lohman, K.K.; Louie, T.; Luzzi, A.; Mägi, R.; Mahajan, A.; Manichaikul, A.W.; McKenzie, C.A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; Mohlke, K. L.; Momozawa, Y.; Morris, A. P.; Murray, A. D.; Nalls, M. A.; Nauck, M.; Nelson, C. P.; North, K. E.; O'Connell, J.R.; Palmer, N.D.; Papanicolau, G.J.; Pedersen, N. L.; Peters, A.; Peyser, P. A.; Polasek, O.; Poulter, N.; Raitakari, O.T.; Reiner, A. P.; Renström, F.; Rice, T.K.; Rich, S.S.; Robinson, J.G.; Rose, L. M.; Rosendaal, F. R.; Rudan, I.; Schmidt, C.O.; Schreiner, P. J.; Scott, W.R.; Sever, P.; Shi, Y.; Sidney, S.; Sims, M.; Smith, J. A.; Snieder, H.; Starr, J. M.; Strauch, K.; Stringham, H. M.; Tan, N. Y. Q.; Tang, H.; Taylor, K. D.; Teo, Y. Y.; Tham, Y. C.; Tiemeier, H.; Turner, S. T.; Uitterlinden, A. G.; Understanding Society Scientific Group; van Heemst, D.; Waldenberger, M.; Wang, H.; Wang, L.; Wang, L.; Wei, W. B.; Williams, C. A.; Wilson, G. Sr.; Wojczynski, M. K.; Yao, J.; Young, K.; Yu, C.; Yuan, J. M.; Zhou, J.; Zonderman, A. B.; Becker, D. M.; Boehnke, M.; Bowden, D. W.; Chambers, J. C.; Cooper, R. S.; de Faire, U.; Deary, I. J.; Elliott, P.; Esko, T.; Farrall, M.; Franks, P. W.; Freedman, B. I.; Froguel, P.; Gasparini, P.; Gieger, C.; Horta, B. L.; Juang, J. J.; Kamatani, Y.; Kammerer, C. M.; Kato, N.; Kooner, J. S.; Laakso, M.; Laurie, C. C.; Lee, I. T.; Lehtimäki, T.; Lifelines Cohort; Magnusson, P. K. E.; Oldehinkel, A. J.; Penninx, B. W. J. H.; Pereira, A. C.; Rauramaa, R.; Redline, S.; Samani, N. J.; Scott, J.; Shu, X. O.; van der Harst, P.; Wagenknecht, L. E.; Wang, J. S.; Wang, Y. X.; Wareham, N. J.; Watkins, H.; Weir, D. R.; Wickremasinghe, A.R.; Wu, T.; Zeggini, E.; Zheng, W.; Bouchard, C.; Evans, M. K.; Gudnason, V.; Kardia, S. L. R.; Liu, Y.; Psaty, B. M.; Ridker, P. M.; van Dam, R. M.; Mook-Kanamori, D. O.; Fornage, M.; Province, M. A.; Kelly, T. N.; Fox, E. R.; Hayward, C.; van Duijn, C. M.; Tai, E. S.; Wong, T. Y.; Loos, R. J. F.; Franceschini, N.; Rotter, J. I.; Zhu, X.; Bierut, L. J.; Gauderman, W. J.; Rice, K.; Munroe, P. B.; Morrison, A. C.; Rao, D. C.; Cupples, L. A.; Rotimi, C. N.
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
(Public Library of Science, 2018) Feitosa, M.F.; Kraja, A.T.; Chasman, D.I.; Sung, Y.J.; Winkler, T.W.; Ntalla, I.; Guo, X.; Franceschini, N.; Cheng, C.Y.; Sim, X.; Vojinovic, D.; Marten, J.; Musani, S.K.; Li, C.; Bentley, A.R.; Brown, M.R.; Scwander, K.; Richard, M.A.; Noordam, R.; Aschard, H.; Bartz, T.M.; Bielak, L.F.; Dorajoo, R.; Fishaer, V.; Hartwig, F.P.; Horimoto, A.R.V.R.; Lohman, K.K.; Manning, A.K.; Rankinen, T.; Smith, A.V.; Tajiddin, S.M.; Wojczynski, M.K.; Alver, M.; Boissel, M.; Cai, Q.; Campbell, A.; Chai, J.F.; Chen, X.; Divers, J.; Gao, C.; Goel, A.; Hagemeijer, Y.; Harris, S.E.; He, M.; Hsu, F.C.; Jackson, A.U.; Kahonen, M.; Kasturiratne, A.; Komulainen, P.; Kuhnel, B.; Laguzzi, F.; Luan, J.; Matoba, N.; Nolte, I.M.; Padmanabhan, S.; Riaz, M.; Rueedi, R.; Robino, A.; Said, M.A.; Scott, R.A.; Soffer, T.; Stancakova, A.; Takeuchi, F.; Tayo, B.O.; van de Most, P.J.; Varga, T.V.; Vitart, V.; Wang, Y.; Ware, E.B.; Warren, H.R.; Weiss, S.; Wen, W.; Yanek, L.R.; Zhang, W.; Zhao, J.H.; Afaq, S.; Amin, N.; Amini, M.; Arking, D.E.; Aung, T.; Boerwinkle, E.; Borecki, I.; Broecki, I.; Broeckel, U.; Brown, M.; Brumat, M.; Burke, G.L.; Canouil, M.; Chakravarthi, A.; Charumathi, S.; Ida Chen, Y.D.; Connel, J.M.; Correa, A.; de Las Fuentes, L.; de Mutsert, R.; de Silva, H.J.; Deng, X.; Ding, J.; Duan, Q.; Eaton, C.B.; Ehret, G.; Eppinga, R.N.; Evangelou, E.; Faul, J.D.; Felix, S.B.; Forouhi, N.G.; Forrester, T.; Franco, O.H.; Friedlander, Y.; Gandin, I.; Gao, H.; Ghanbari, M.; Gigante, B.; Gu, C.C.; Gu, D.; Hagenaars, S.P.; Halmans, G.; Harris, T.B.; He, J.; Heikkinen, S.; Heng, C.K.; Hirata, M.; Howard, B.V.; Ikram, M.A.; InterAct Consortium; John, U.; Katsuya, T.; Lakka, T.A.; Langefeld, C.D.; Langenberg, C.; Launer, L.J.; Lehne, B.; Lewis, C.E.; Li, Y.; Lin, S.; Lin, U.; Liu, J.; Liu, J.; Loh, M.; Louie, T.; Magi, R.; McKenzie, C.A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; mohlke, K.L.; Momozawa, Y.; Nalls, M.A.; Nelson, C.P.; Sotoodehnia, N.; Norris, J.M.; O'Connel, J.R.; Palmer, N.D.; Perls, T.; Pedersen, N.L.; Peters, A.; Peyser, P.A.; Poulter, N.; Raffel, L.J.; Raitakari, O.T.; Roll, K.; Rose, L.M.; Rosendaal, F.R.; Rotter, J.I.; Schimidit, C.O.; Schreiner, P.J.; Schupf, N.; Scott, W.R.; Sever, P.S.; Shi, Y.; Sidney, S.; Sims, M.; Sitlani, C.M.; Smith, J.A.; Snieder, H.; Starr, J.M.; Strauch, K.; Stringham, H.M.; Tan, N.Y.Q.; Tang, H.; Taylor, K.D.; Teo, Y.Y.; Tham, Y.C.; Turner, S.C.; Uitterlinden, A.G.; Vollenweider, P.; Waldenberger, M.; Wang, L.; Wang, Y.X.; Wei, W.B.; Williams, C.; Yao, J.; Yuan, J.M.; Zhao, W.; Zonderman, A.B.; Becker, D.M.; Boehnke, M.; Bowden, D.W.; Chambers, J.C.; Deary, I.J.; Esco, T.; Farall, M.; Frankd, P.W.; Freedman, B.I.; Froguel, P.; Gasparini, P.; Gieger, C.; Jonas, J.B.; Kamatani, Y.; Kato, N.; Kooner, J.S.; Kutalik, Z.; Laakso, M.; Laurie, C.C.; Leander, K.; Lehtimaki, T.; Study, L.C.; Magnusson, P.K.E.; Olderhinkel, A.J.; Penninx, B.W.J.H.; Polasek, O.; Porteous, D.J.; Rauramaa, R.; Ssamani, N.J.; Scott, J.; Shu, X.O.; van der Harst, P.; Wagenknecht, L.E.; Wareham, N.J.; Watkins, H.; Weir, D.R.; Wickremasinghe, A.R.; Wu, T.; Zheng, W.; Bouchard, C.; Christensen, K.; Evans, M.K.; Gudnason, V.; Horta, B.L.; Kardia, S.L.R.; Liu, Y.; Pereira, A.C.; Psaty, B.M.; Ridker, P.M.; van Dam, R.M.; Gauderman, W.J.; Zhu, X.; Mook-Kanamori, D.O.; Fornage, M.; Rotimi, C.N.; Cupples, L.A.; Kelly, T.N.; Fox, E.R.; Hayward, C.; van Duijn, C.M.; Tai, E.S.; Wong, T.Y.; Kooperberg, C.; Palmas, W.; Rice, K.; Morrison, A.C.; Elliott, P.; Caulfield, M.J.; Munroe, P.B.; Rao, D.C.; Province, M.A.; Levy, D.
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension
A saturated map of common genetic variants associated with human height
(Nature Publishing Group, 2022) 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.; 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.; Ha, 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.; 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, E.R.B.; 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, R.A.J.; Smith, A.V.; Smith, J.A.; Smyth, L.J.; Southam, L.; Steinthorsdottir, V.; Sun, L.; Takeuchi, F.; Tallapragada, D.S.P.; Taylor, K.D.; Tayo, B.O.; Tcheandjieu, C.; Terzikhan, N.; Tesolin, P.; Teumer, A.; Theusch, E.; Thompson, D.J.; Thorleifsson, G.; Timmers, P.R.H.J.; 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. 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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 sizes1. 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 panel2) 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.
Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage
(New York, Academic Press, 2015) Phan, T.G.; Mori, D.; Deng, X.; Rajindrajith, S.; Ranawaka, U.; Fan Ng, T.F.; Bucardo-Rivera, F.; Orlandi, P.; Ahmed, K.; Delwart, E.
Viruses with small circular ssDNA genomes encoding a replication initiator protein can infect a wide range of eukaryotic organisms ranging from mammals to fungi. The genomes of two such viruses, a cyclovirus (CyCV-SL) and gemycircularvirus (GemyCV-SL) were detected by deep sequencing of the cerebrospinal fluids of Sri Lankan patients with unexplained encephalitis. One and three out of 201 CSF samples (1.5%) from unexplained encephalitis patients tested by PCR were CyCV-SL and GemyCV-SL DNA positive respectively. Nucleotide similarity searches of pre-existing metagenomics datasets revealed closely related genomes in feces from unexplained cases of diarrhea from Nicaragua and Brazil and in untreated sewage from Nepal. Whether the tropism of the cyclovirus and gemycircularvirus reported here include humans or other cellular sources in or on the human body remains to be determined.