Browsing by Author "Jiang, Y."

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    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. W.; Zhou, W.; Zimmermann, M.E.; Zoledziewska, M.; Adair, L.S.; Adams, H.H.H.; Aguilar-Salinas, C.A.; Al-Mulla, F.; Arnett, D.K.; 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, L.C.P.G.M.; de Jager, P.L.; de Kleijn, D.P.V.; de Silva, H.J.; Dedoussis, G.V.; den Hollander, A.I.; Du, S.; Easton, D.F.; Elders, P.J.M.; 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, S.F.A.; 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, S.L.R.; Karpe, F.; Kato, N.; Kee, F.; Kessler, T.; Khera, A.V.; Khor, C.C.; Kiemeney, L.A.L.M.; 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.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Magnusson, P.K.E.; Marcus, G.M.; Vidal, P.M.; Martin, N.G.; Martin, N.G.; Lieb, W.; Lin, X.; Lind, L.; Linneberg, A.; Liu, C.T.; Liu, J.; Loeffler, M.; London, B.; Lubitz, S.A.; Lye, S.J.; Mackey, D.A.; Mägi, R.; Mägi, R.; Magnusson, P.K.E.; 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.; Oldehinkel, A.J.; Orozco, L.; Pahkala, K.; Pajukanta, P.; Palmer, C.N.A.; Parra, E.J.; Pattaro, C.; Pedersen, O.; Pennell, C.E.; Penninx, B.W.J.H.; 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.; 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.; Chasman, D.I.; Cho, Y.S.; Heid, I.M.; McCarthy, M.I.; Ng, M.C.Y.; 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, R.J.F.; Mohlke, K.L.; North, K.E.; Stefansson, K.; Walters R.G.v.; Winkler, T.W.; Young, K.L.; Loh, P.R.; Yang, J.; Esko, T.; Assimes, T.L.; Auton, A.; Abecasis, G.R.; Willer, C.J.; Locke, A.E.; Berndt, S.I.; Lettre, G.; Frayling, T.M.; Frayling, T.M.; Okada, Y.; Wood, A.R.; Visscher, P.M.; Hirschhorn, J.N.
    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.
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    The third intensive care bundle with blood pressure reduction in acute cerebral haemorrhage trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
    (Elsevier, 2023) Ma, L.; Hu, X.; Song, L.; Chen, X.; Ouyang, M.; Billot, L.; Li, Q.; Malavera, A.; Li, X.; Muñoz-Venturelli, P.; de Silva, A.; Thang, N.H.; Wahab, K.W.; Pandian, J.D.; Wasay, M.; Pontes-Neto, O.M.; Abanto, C.; Arauz, A.; Shi, H.; Tang, G.; Zhu, S.; She, X.; Liu, L.; Sakamoto, Y.; You, S.; Han, Q.; Crutzen, B.; Cheung, E.; Li, Y.; Wang, X.; Chen, C.; Liu, F.; Zhao, Y.; Li, H.; Liu, Y.; Jiang, Y.; Chen, L.; Wu, B.; Liu, M.; Xu, J.; You, C.; Anderson, C.S.; INTERACT3 Investigators
    BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.