464 results on '"Denny, JC."'
Search Results
2. Genetic variation in the HLA region is associated with susceptibility to herpes zoster
- Author
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Crosslin, DR, Carrell, DS, Burt, A, Kim, DS, Underwood, JG, Hanna, DS, Comstock, BA, Baldwin, E, de Andrade, M, Kullo, IJ, Tromp, G, Kuivaniemi, H, Borthwick, KM, McCarty, CA, Peissig, PL, Doheny, KF, Pugh, E, Kho, A, Pacheco, J, Hayes, MG, Ritchie, MD, Verma, SS, Armstrong, G, Stallings, S, Denny, JC, Carroll, RJ, Crawford, DC, Crane, PK, Mukherjee, S, Bottinger, E, Li, R, Keating, B, Mirel, DB, Carlson, CS, Harley, JB, Larson, EB, and Jarvik, GP
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Immunology ,HIV/AIDS ,Human Genome ,Infectious Diseases ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Age of Onset ,Aged ,Algorithms ,Cohort Studies ,Electronic Health Records ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Herpes Zoster ,Herpesvirus 3 ,Human ,Humans ,Male ,Middle Aged ,RNA ,Long Noncoding ,RNA ,Untranslated ,Retrospective Studies ,United States - Abstract
Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.
- Published
- 2015
3. Characterization of Statin Dose Response in Electronic Medical Records
- Author
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Wei, W‐Q, Feng, Q, Jiang, L, Waitara, MS, Iwuchukwu, OF, Roden, DM, Jiang, M, Xu, H, Krauss, RM, Rotter, JI, Nickerson, DA, Davis, RL, Berg, RL, Peissig, PL, McCarty, CA, Wilke, RA, and Denny, JC
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Human Genome ,Clinical Research ,Genetics ,Algorithms ,Alleles ,Atorvastatin ,Cholesterol ,LDL ,Cohort Studies ,Databases ,Factual ,Dose-Response Relationship ,Drug ,Electronic Health Records ,Genotype ,Heptanoic Acids ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hyperlipidemias ,Lipid Metabolism ,Lipids ,Phenotype ,Polymorphism ,Single Nucleotide ,Pyrroles ,Randomized Controlled Trials as Topic ,Simvastatin ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences - Abstract
Efforts to define the genetic architecture underlying variable statin response have met with limited success, possibly because previous studies were limited to effect based on a single dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in subjects homozygous for the minor allele vs. 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand the genetic factors contributing to drug response.
- Published
- 2014
4. Defining the role of common variation in the genomic and biological architecture of adult human height
- Author
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Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Medical Research Council (MRC), APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING DUISTERMAAT, Jj, James, Al, Johansson, A, Kho, An, Magnusson, Pk, Mcardle, Wl, Mckenzie, Ca, Mclaren, Pj, Monda, Kl, Morken, Ma, MÜLLER NURASYID, M, Musk, Aw, Nolte, Im, Nöthen, Mm, Rayner, Nw, Robertson, Nr, Rose, Lm, Schumacher, Fr, Scott, Ra, Smit, Jh, Smith, Av, Stanton, Av, Stott, Dj, Stringham, Hm, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Tyrer, Jp, VAN DIJK, S, VAN SCHOOR, Nm, VAN DER VELDE, N, VAN HEEMST, D, VAN OORT, Fv, Vermeulen, Sh, Vonk, Jm, Waite, Ll, Wilkens, Lr, Wojczynski, Mk, Wright, Af, Bakker, Sj, Bergman, Rn, Boomsma, Di, Bornstein, Sr, Brown, Mj, Caulfield, Mj, Crawford, Dc, Cupples, La, DE FAIRE, U, DEN RUIJTER, Hm, Eriksson, Jg, Forouhi, Ng, Gansevoort, Rt, Gejman, Pv, Haas, Dw, Harris, Tb, Hattersley, At, Heath, Ac, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hovingh, Gk, Humphries, Se, Hunt, Sc, Jacobs, Kb, Jarvelin, Mr, Jula, Am, Kastelein, Jj, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Kraja, At, Lakka, Ta, LE MARCHAND, L, Madden, Pa, Manunta, Paolo, Matise, Tc, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
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Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,Medizin ,Genome-wide association study ,Adult ,Analysis of Variance ,Body Height/genetics ,European Continental Ancestry Group/genetics ,Genetic Variation/genetics ,Genetics, Population ,Genome-Wide Association Study/methods ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism, Single Nucleotide/genetics ,heritability ,0302 clinical medicine ,Genome-wide ,SNPS ,snps ,Genetics & Heredity ,ddc:616 ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,variants ,GENETIC-VARIATION ,Biological Sciences ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,body height ,genetic-variation ,Life Sciences & Biomedicine ,Single Nucleotide/genetics ,Human ,European Continental Ancestry Group ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,NO ,complex traits ,03 medical and health sciences ,Genetic variation ,heritability, adult, height ,Polymorphism ,Human height ,PAGEGE Consortium ,education ,Gene ,VLAG ,030304 developmental biology ,Global Nutrition ,Wereldvoeding ,genome-wide association study ,Science & Technology ,Whites ,Oligonucleotide Array Sequence Analysi ,MUTATIONS ,COMPLEX TRAITS ,ta1184 ,Klinisk medicin ,population genetics ,Genetic Variation ,Heritability ,ta3121 ,mutations ,Genetic architecture ,Body Height ,genetic variation ,MIGen Consortium ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Clinical Medicine ,030217 neurology & neurosurgery ,height ,LifeLines Cohort Study ,Developmental Biology ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
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5. A Polygenic and Phenotypic Risk Prediction for Polycystic Ovary Syndrome Evaluated by Phenome-Wide Association Studies
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Joo, YY, Actkins, K, Pacheco, JA, Basile, AO, Carroll, R, Crosslin, DR, Day, F, Denny, JC, Edwards, D R V, Hakonarson, H, Harley, JB, Hebbring, S J, Ho, K, Jarvik, GP, Jones, M, Karaderi, T, Mentch, FD, Meun, Cindy, Namjou, B, Pendergrass, S, Ritchie, MD, Stanaway, IB, Urbanek, M, Walunas, TL, Smith, M, Chisholm, RL, Kho, AN, Davis, L, Hayes, MG, Joo, YY, Actkins, K, Pacheco, JA, Basile, AO, Carroll, R, Crosslin, DR, Day, F, Denny, JC, Edwards, D R V, Hakonarson, H, Harley, JB, Hebbring, S J, Ho, K, Jarvik, GP, Jones, M, Karaderi, T, Mentch, FD, Meun, Cindy, Namjou, B, Pendergrass, S, Ritchie, MD, Stanaway, IB, Urbanek, M, Walunas, TL, Smith, M, Chisholm, RL, Kho, AN, Davis, L, and Hayes, MG
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- 2020
6. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)
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Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
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- 2018
7. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)
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Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
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- 2018
8. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- Author
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Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, Sheth, K, Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, and Sheth, K
- Abstract
OBJECTIVE: We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. METHODS: We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. RESULTS: We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10-4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10-48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1). CONCLUSIONS: Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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- 2018
9. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
- Author
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van Setten, J, Brody, JA, Jamshidi, Y, Swenson, B R, Butler, AM, Campbell, H, Del Greco, FM, Evans, DS, Gibson, Q, Gudbjartsson, DF, Kerr, KF, Krijthe, Bouwe, Lyytikainen, LP, Muller, C, Muller-Nurasyid, M, Nolte, IM, Padmanabhan, S, Ritchie, MD, Robino, A, Smith, AV, Steri, M, Tanaka, T, Teumer, A, Trompet, S, Ulivi, S, Verweij, N, Yin, XY, Arnar, DO, Asselbergs, FW, Bader, JS, Barnard, J, Bis, J, Blankenberg, S, Boerwinkle, E, Bradford, Y, Buckley, BM, Chung, MK, Crawford, D, den Hoed, M, Denny, JC, Dominiczak, AF, Ehret, GB, Eijgelsheim, Mark, Ellinor, PT, Felix, SB, Franco Duran, OH, Franke, L, Harris, TB, Holm, H, Ilaria, G, Iorio, A, Kahonen, M, Kolcic, I, Kors, Jan, Lakatta, EG, Launer, LJ, Lin, HH, Lin, H J, Loos, RJF, Lubitz, SA, Macfarlane, PW, Magnani, JW, Leach, IM, Meitinger, T, Mitchell, BD, Munzel, T, Papanicolaou, G J, Peters, A, Pfeufer, A, Pramstaller, PP, Raitakari, OT, Rotter, JI, Rudan, I, Samani, NJ, Schlessinger, D, Silva Aldana, Claudia, Sinner, MF, Smith, JD, Snieder, H, Soliman, EZ, Spector, TD, Stott, DJ, Strauch, K, Tarasov, KV, Thorsteinsdottir, U, Uitterlinden, André, Van Wagoner, DR, Volker, U, Volzke, H, Waldenberger, M, Westra, HJ, Wild, PS, Zeller, T, Alonso, A, Avery, CL, Bandinelli, S, Benjamin, EJ, Cucca, F, Dorr, M, Ferrucci, L, Gasparini, P, Gudnason, V, Hayward, C, Heckbert, SR, Hicks, AA, Jukema, JW, Kaab, S, Lehtimaki, T, Liu, YM, Munroe, PB, Parsa, A, Polasek, O, Psaty, BM, Roden, DM, Schnabel, RB, Sinagra, G, Stefansson, K, Stricker, Bruno, van der Harst, P, Duijn, Cornelia, Wilson, JF, Gharib, SA, de Bakker, PIW, Isaacs, A, Arking, DE, Sotoodehnia, N, van Setten, J, Brody, JA, Jamshidi, Y, Swenson, B R, Butler, AM, Campbell, H, Del Greco, FM, Evans, DS, Gibson, Q, Gudbjartsson, DF, Kerr, KF, Krijthe, Bouwe, Lyytikainen, LP, Muller, C, Muller-Nurasyid, M, Nolte, IM, Padmanabhan, S, Ritchie, MD, Robino, A, Smith, AV, Steri, M, Tanaka, T, Teumer, A, Trompet, S, Ulivi, S, Verweij, N, Yin, XY, Arnar, DO, Asselbergs, FW, Bader, JS, Barnard, J, Bis, J, Blankenberg, S, Boerwinkle, E, Bradford, Y, Buckley, BM, Chung, MK, Crawford, D, den Hoed, M, Denny, JC, Dominiczak, AF, Ehret, GB, Eijgelsheim, Mark, Ellinor, PT, Felix, SB, Franco Duran, OH, Franke, L, Harris, TB, Holm, H, Ilaria, G, Iorio, A, Kahonen, M, Kolcic, I, Kors, Jan, Lakatta, EG, Launer, LJ, Lin, HH, Lin, H J, Loos, RJF, Lubitz, SA, Macfarlane, PW, Magnani, JW, Leach, IM, Meitinger, T, Mitchell, BD, Munzel, T, Papanicolaou, G J, Peters, A, Pfeufer, A, Pramstaller, PP, Raitakari, OT, Rotter, JI, Rudan, I, Samani, NJ, Schlessinger, D, Silva Aldana, Claudia, Sinner, MF, Smith, JD, Snieder, H, Soliman, EZ, Spector, TD, Stott, DJ, Strauch, K, Tarasov, KV, Thorsteinsdottir, U, Uitterlinden, André, Van Wagoner, DR, Volker, U, Volzke, H, Waldenberger, M, Westra, HJ, Wild, PS, Zeller, T, Alonso, A, Avery, CL, Bandinelli, S, Benjamin, EJ, Cucca, F, Dorr, M, Ferrucci, L, Gasparini, P, Gudnason, V, Hayward, C, Heckbert, SR, Hicks, AA, Jukema, JW, Kaab, S, Lehtimaki, T, Liu, YM, Munroe, PB, Parsa, A, Polasek, O, Psaty, BM, Roden, DM, Schnabel, RB, Sinagra, G, Stefansson, K, Stricker, Bruno, van der Harst, P, Duijn, Cornelia, Wilson, JF, Gharib, SA, de Bakker, PIW, Isaacs, A, Arking, DE, and Sotoodehnia, N
- Published
- 2018
10. Biological interpretation of genome-wide association studies using predicted gene functions
- Author
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Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Chu AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Mägi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AA, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Mateo Leach I, Medina Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Ärnlöv J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blüher M, Bolton JL, Böttcher Y, Boyd HA, Bruinenberg M, Buckley BM, Buyske S, Caspersen IH, Chines PS, Clarke R, Claudi Boehm S, Cooper M, Daw EW, De Jong A, Deelen J, Delgado G, Denny JC, Dhonukshe Rutten R, Dimitriou M, Doney AS, Dörr M, Eklund N, Eury E, Folkersen L, Garcia ME, Geller F, Giedraitis V, Go AS, Grallert H, Grammer TB, Gräßler J, Grönberg H, de Groot LC, Groves CJ, Haessler J, Haller T, Hallmans G, Hannemann A, Hartman CA, Hassinen M, Hayward C, Heard Costa NL, Helmer Q, Hemani G, Henders AK, Hillege HL, Hlatky MA, Hoffmann W, Hoffmann P, Holmen O, Houwing Duistermaat JJ, Illig T, Isaacs A, James AL, Jeff J, Johansen B, Johansson Å, Jolley J, Juliusdottir T, Junttila J, Kho AN, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Lindström J, Lobbens S, Lorentzon M, Lu Y, Lyssenko V, Magnusson PK, Mahajan A, Maillard M, McArdle WL, McKenzie CA, McLachlan S, McLaren PJ, Menni C, Merger S, Milani L, Moayyeri A, Monda KL, Morken MA, Müller G, Müller Nurasyid M, Musk AW, Narisu N, Nauck M, Nolte IM, Nöthen MM, Oozageer L, Pilz S, Rayner NW, Renstrom F, Robertson NR, Rose LM, Roussel R, Sanna S, Scharnagl H, Scholtens S, Schumacher FR, Schunkert H, Scott RA, Sehmi J, Seufferlein T, Shi J, Silventoinen K, Smit JH, Smith AV, Smolonska J, Stanton AV, Stirrups K, Stott DJ, Stringham HM, Sundström J, Swertz MA, Syvänen AC, Tayo BO, Thorleifsson G, Tyrer JP, van Dijk S, van Schoor NM, van der Velde N, van Heemst D, van Oort FV, Vermeulen SH, Verweij N, Vonk JM, Waite LL, Waldenberger M, Wennauer R, Wilkens LR, Willenborg C, Wilsgaard T, Wojczynski MK, Wong A, Wright AF, Zhang Q, Arveiler D, Bakker SJ, Beilby J, Bergman RN, Bergmann S, Biffar R, Blangero J, Boomsma I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, Brown MJ, Campbell H, Caulfield MJ, Chakravarti A, Collins R, Collins FS, Crawford DC, Cupples LA, Danesh J, de Faire U, den Ruijter HM, Erbel R, Erdmann J, Eriksson JG, Farrall M, Ferrannini E, Ferrières J, Ford I, Forouhi NG, Forrester T, Gansevoort RT, Gejman PV, Gieger C, Golay A, Gottesman O, Gudnason V, Gyllensten U, Haas DW, Hall AS, Harris TB, Hattersley AT, Heath AC, Hengstenberg C, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Hovingh GK, Humphries SE, Hunt SC, Hypponen E, Jacobs KB, Jarvelin MR, Jousilahti P, Jula AM, Kaprio J, Kastelein JJ, Kayser M, Kee F, Keinanen Kiukaanniemi SM, Kiemeney LA, Kooner JS, Kooperberg C, Koskinen S, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Le Marchand L, Lehtimäki T, Lupoli S, Madden PA, Männistö S, Manunta P, Marette A, Matise TC, McKnight B, Meitinger T, Moll FL, Montgomery GW, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Ouwehand WH, Pasterkamp G, Peters A, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ritchie M, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schwarz PE, Sebert S, Sever P, Shuldiner AR, Sinisalo J, Steinthorsdottir V, Stolk RP, Tardif JC, Tönjes A, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PI, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hayes MG, Hui J, Hunter DJ, Hveem K, Jukema JW, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, März W, Melbye M, Moebus S, Munroe PB, Njølstad I, Oostra BA, Palmer CN, Pedersen NL, Perola M, Pérusse L, Peters U, Powell JE, Power C, Quertermous T, Rauramaa R, Reinmaa E, Ridker PM, Rivadeneira F, Rotter JI, Saaristo TE, Saleheen D, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Strauch K, Stumvoll M, Tuomilehto J, Uusitupa M, van der Harst P, Völzke H, Walker M, Wareham NJ, Watkins H, Wichmann HE, Wilson JF, Zanen P, Deloukas P, Heid IM, Lindgren CM, Mohlke KL, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, Frayling T.M., Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wood, AR., Esko, T., Yang, J., Vedantam, S., Pers, TH., Gustafsson, S., Chu, AY., Estrada, K., Luan£££Jian'an£££ J., Kutalik£££Zoltán£££ Z., Amin, N., Buchkovich, ML., Croteau-Chonka, DC., Day, FR., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, AU., Karjalainen, J., Lo, KS., Locke, AE., Mägi, R., Mihailov, E., Porcu, E., Randall, JC., Scherag, A., Vinkhuyzen, AA., Westra, HJ., Winkler, TW., Workalemahu, T., Zhao, JH., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, GB., Feenstra, B., Feitosa, MF., Fischer, K., Fraser, RM., Goel, A., Gong, J., Justice, E., Kanoni, S., Kleber, ME., Kristiansson, K., Lim, U., Lotay, V., Lui, JC., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, MA., Nyholt, DR., Palmer, CD., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, JS., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, RJ., Sung, YJ., Tanaka, T., Teumer, A., Trompet, S., van der Laan SW., van Setten, J., Van Vliet-Ostaptchouk JV., Wang, Z., Yengo£££Loïc£££ L., Zhang, W., Afzal, U., Ärnlöv, J., Arscott, GM., Bandinelli, S., Barrett, A., Bellis, C., Bennett, AJ., Berne, C., Blüher, M., Bolton, JL., Böttcher, Y., Boyd, HA., Bruinenberg, M., Buckley, BM., Buyske, S., Caspersen, IH., Chines, PS., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, EW., De Jong, A., Deelen, J., Delgado, G., Denny, JC., Dhonukshe-Rutten, R., Dimitriou, M., Doney, AS., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, ME., Geller, F., Giedraitis, V., Go, AS., Grallert, H., Grammer, TB., Gräßler, J., Grönberg, H., de Groot LC., Groves, CJ., Haessler, J., Haller, T., Hallmans, G., Hannemann, A., Hartman, CA., Hassinen, M., Hayward, C., Heard-Costa, NL., Helmer, Q., Hemani, G., Henders, AK., Hillege, HL., Hlatky, MA., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, JJ., Illig, T., Isaacs, A., James, AL., Jeff, J., Johansen, B., Johansson£££Åsa£££ Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, AN., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, PK., Mahajan, A., Maillard, M., McArdle, WL., McKenzie, CA., McLachlan, S., McLaren, PJ., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, KL., Morken, MA., Müller, G., Müller-Nurasyid, M., Musk, AW., Narisu, N., Nauck, M., Nolte, IM., Nöthen, MM., Oozageer, L., Pilz, S., Rayner, NW., Renstrom, F., Robertson, NR., Rose, LM., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, FR., Schunkert, H., Scott, RA., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, JH., Smith, AV., Smolonska, J., Stanton, AV., Stirrups, K., Stott, DJ., Stringham, HM., Sundström, J., Swertz, MA., Syvänen, AC., Tayo, BO., Thorleifsson, G., Tyrer, JP., van Dijk, S., van Schoor NM., van der Velde, N., van Heemst, D., van Oort FV., Vermeulen, SH., Verweij, N., Vonk, JM., Waite, LL., Waldenberger, M., Wennauer, R., Wilkens, LR., Willenborg, C., Wilsgaard, T., Wojczynski, MK., Wong, A., Wright, AF., Zhang, Q., Arveiler, D., Bakker, SJ., Beilby, J., Bergman, RN., Bergmann, S., Biffar, R., Blangero, J., Boomsma, I., Bornstein, SR., Bovet, P., Brambilla, P., Brown, MJ., Campbell, H., Caulfield, MJ., Chakravarti, A., Collins, R., Collins, FS., Crawford, DC., Cupples, LA., Danesh, J., de Faire, U., den Ruijter HM., Erbel, R., Erdmann, J., Eriksson, JG., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, NG., Forrester, T., Gansevoort, RT., Gejman, PV., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, DW., Hall, AS., Harris, TB., Hattersley, AT., Heath, AC., Hengstenberg, C., Hicks, AA., Hindorff, LA., Hingorani, AD., Hofman, A., Hovingh, GK., Humphries, SE., Hunt, SC., Hypponen, E., Jacobs, KB., Jarvelin, MR., Jousilahti, P., Jula, AM., Kaprio, J., Kastelein, JJ., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, SM., Kiemeney, LA., Kooner, JS., Kooperberg, C., Koskinen, S., Kovacs, P., Kraja, AT., Kumari, M., Kuusisto, J., Lakka, TA., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, PA., Männistö, S., Manunta, P., Marette, A., Matise, TC., McKnight, B., Meitinger, T., Moll, FL., Montgomery, GW., Morris, AD., Morris, AP., Murray, JC., Nelis, M., Ohlsson, C., Oldehinkel, AJ., Ong, KK., Ouwehand, WH., Pasterkamp, G., Peters, A., Pramstaller, PP., Price, JF., Qi, L., Raitakari, OT., Rankinen, T., Rao, DC., Rice, TK., Ritchie, M., Rudan, I., Salomaa, V., Samani, NJ., Saramies, J., Sarzynski, MA., Schwarz, PE., Sebert, S., Sever, P., Shuldiner, AR., Sinisalo, J., Steinthorsdottir, V., Stolk, RP., Tardif, JC., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, MC., Amouyel, P., Asselbergs, FW., Assimes, TL., Bochud, M., Boehm, BO., Boerwinkle, E., Bottinger, EP., Bouchard, C., Cauchi, S., Chambers, JC., Chanock, SJ., Cooper, RS., de Bakker PI., Dedoussis, G., Ferrucci, L., Franks, PW., Froguel, P., Groop, LC., Haiman, CA., Hamsten, A., Hayes, MG., Hui, J., Hunter, DJ., Hveem, K., Jukema, JW., Kaplan, RC., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, NG., März, W., Melbye, M., Moebus, S., Munroe, PB., Njølstad, I., Oostra, BA., Palmer, CN., Pedersen, NL., Perola, M., Pérusse, L., Peters, U., Powell, JE., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, PM., Rivadeneira, F., Rotter, JI., Saaristo, TE., Saleheen, D., Schlessinger, D., Slagboom, PE., Snieder, H., Spector, TD., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., van der Harst, P., Völzke, H., Walker, M., Wareham, NJ., Watkins, H., Wichmann, HE., Wilson, JF., Zanen, P., Deloukas, P., Heid, IM., Lindgren, CM., Mohlke, KL., Speliotes, EK., Thorsteinsdottir, U., Barroso£££Inês£££ I., Fox, CS., North, KE., Strachan, DP., Beckmann, JS., Berndt, SI., Boehnke, M., Borecki, IB., McCarthy, MI., Metspalu, A., Stefansson, K., Uitterlinden, AG., van Duijn CM., Franke, L., Willer, CJ., Price, AL., Lettre, G., Loos, RJ., Weedon, MN., Ingelsson, E., O'Connell, JR., Abecasis, GR., Chasman, DI., Goddard, ME., Visscher, PM., Hirschhorn, JN., Frayling, TM., Clinicum, Jaakko Kaprio / Principal Investigator, Department of Public Health, Institute for Molecular Medicine Finland, Genetic Epidemiology, Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, A, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, de Groot, L, Groves, C, Haessler, J, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, van Dijk, S, van Schoor, N, van der Velde, N, van Heemst, D, van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, I, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, de Faire, U, den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Pers, Th, Karjalainen, Jm, Westra, Hj, Wood, Ar, Lui, Jc, Speliotes, Ek, Hirschhorn, Jn, and Faculty of Health Sciences
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Cell type ,Candidate gene ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,LOCI ,General Physics and Astronomy ,Genome-wide association study ,Disease ,Computational biology ,Biology ,Research Support ,General Biochemistry, Genetics and Molecular Biology ,Article ,DISEASE ,N.I.H ,CANDIDATE GENES ,Genome-Wide Association Study/methods ,Software ,HEIGHT ,Research Support, N.I.H., Extramural ,Genetics ,Journal Article ,NETWORK ,Non-U.S. Gov't ,Gene ,COMMON ,Intramural ,ARCHITECTURE ,Biochemistry, Genetics and Molecular Biology (all) ,Multidisciplinary ,IDENTIFICATION ,ta1184 ,Research Support, Non-U.S. Gov't ,Gene sets ,Extramural ,General Chemistry ,ta3121 ,Research Support, N.I.H., Intramural ,Phenotype ,3142 Public health care science, environmental and occupational health ,Biological sciences ,DATA SETS ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Identification (biology) ,INTEGRATION ,Genome-Wide Association Study - Abstract
Article, The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes., published version, http://purl.org/eprint/status/PeerReviewed
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- 2015
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11. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium
- Author
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Weng, LC, Lunetta, KL, Muller-Nurasyid, M, Smith, AV, Theriault, S, Weeke, PE, Barnard, J, Bis, JC, Lyytikainen, LP, Kleber, ME, Martinsson, A, Lin, H J, Rienstra, M, Trompet, S, Krijthe, Bouwe, Dorr, M, Klarin, D, Chasman, DI, Sinner, MF, Waldenberger, M, Launer, LJ, Harris, TB, Soliman, EZ, Alonso, A, Pare, G, Teixeira, PL, Denny, JC, Shoemaker, MB, Van Wagoner, DR, Smith, JD, Psaty, BM, Sotoodehnia, N, Taylor, KD, Kahonen, M, Nikus, K, Delgado, GE, Melander, O, Engstrom, G, Yao, J, Guo, XQ, Christophersen, IE, Ellinor, PT, Geelhoed, B, Verweij, N (Niek), Macfarlane, P, Ford, I, Heeringa, Jan, Franco Duran, OH, Uitterlinden, André, Volker, U, Teumer, A, Rose, LM, Kaab, S, Gudnason, V, Arking, DE, Conen, D, Roden, DM, Chung, MK, Heckbert, SR, Benjamin, EJ, Lehtimaki, T, Marz, W, Smith, JG, Rotter, JI, van der Harst, P, Jukema, JW, Stricker, Bruno, Felix, SB, Albert, CM, Lubitz, SA, Weng, LC, Lunetta, KL, Muller-Nurasyid, M, Smith, AV, Theriault, S, Weeke, PE, Barnard, J, Bis, JC, Lyytikainen, LP, Kleber, ME, Martinsson, A, Lin, H J, Rienstra, M, Trompet, S, Krijthe, Bouwe, Dorr, M, Klarin, D, Chasman, DI, Sinner, MF, Waldenberger, M, Launer, LJ, Harris, TB, Soliman, EZ, Alonso, A, Pare, G, Teixeira, PL, Denny, JC, Shoemaker, MB, Van Wagoner, DR, Smith, JD, Psaty, BM, Sotoodehnia, N, Taylor, KD, Kahonen, M, Nikus, K, Delgado, GE, Melander, O, Engstrom, G, Yao, J, Guo, XQ, Christophersen, IE, Ellinor, PT, Geelhoed, B, Verweij, N (Niek), Macfarlane, P, Ford, I, Heeringa, Jan, Franco Duran, OH, Uitterlinden, André, Volker, U, Teumer, A, Rose, LM, Kaab, S, Gudnason, V, Arking, DE, Conen, D, Roden, DM, Chung, MK, Heckbert, SR, Benjamin, EJ, Lehtimaki, T, Marz, W, Smith, JG, Rotter, JI, van der Harst, P, Jukema, JW, Stricker, Bruno, Felix, SB, Albert, CM, and Lubitz, SA
- Published
- 2017
12. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study
- Author
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Schmidt, AF, Swerdlow, DI, Holmes, MV, Patel, RS, Fairhurst-Hunter, Z, Lyall, DM, Hartwig, FP, Horta, BL, Hypponen, E, Power, C, Moldovan, M, van Iperen, E, Hovingh, GK, Demuth, I, Norman, K, Steinhagen-Thiessen, E, Demuth, J, Bertram, L, Liu, T, Coassin, S, Willeit, J, Kiechl, S, Willeit, K, Mason, D, Wright, J, Morris, R, Wanamethee, G, Whincup, P, Ben-Shlomo, Y, McLachlan, S, Price, JF, Kivimaki, M, Welch, C, Sanchez-Galvez, A, Marques-Vidal, P, Nicolaides, A, Panayiotou, AG, Onland-Moret, NC, van der Schouw, YT, Matullo, G, Fiorito, G, Guarrera, S, Sacerdote, C, Wareham, NJ, Langenberg, C, Scott, R, Luan, JA, Bobak, M, Malyutina, SA, Pajak, A, Kubinova, R, Tamosiunas, A, Pikhart, H, Husemoen, LLN, Grarup, N, Pedersen, O, Hansen, T, Linneberg, A, Simonsen, KS, Cooper, J, Humphries, SE, Brilliant, M, Kitchner, T, Hakonarson, H, Carrell, DS, McCarty, CA, Kirchner, HL, Larson, EB, Crosslin, DR, de Andrade, M, Roden, DM, Denny, JC, Carty, C, Hancock, S, Attia, J, Holliday, E, Donnell, MO, Yusuf, S, Chong, M, Pare, G, van der Harst, P, Said, MA, Eppinga, RN, Verweij, N, Snieder, H, Christen, T, Mook-Kanamori, DO, Gustafsson, S, Lind, L, Ingelsson, E, Pazoki, Raha, Franco Duran, OH, Hofman, Bert, Uitterlinden, André, Dehghan, Abbas, Teumer, A, Baumeister, S, Dorr, M, Lerch, MM, Volker, U, Volzke, H, Ward, J, Pell, JP, Smith, Derek, Meade, T, Zee, AH, Baranova, EV, Young, R, Ford, I, Campbell, A (Archie), Padmanabhan, S, Bots, ML, Grobbee, DE, Froguel, P, Thuillier, D, Balkau, B, Bonnefond, A, Cariou, B, Smart, M, Bao, Y, Kumari, M, Mahajan, A, Ridker, PM, Chasman, DI, Reiner, AP, Lange, LA, Ritchie, MD, Asselbergs, FW, Casas, JP, Keating, BJ, Preiss, D, Hingorani, AD, Sattar, N, Schmidt, AF, Swerdlow, DI, Holmes, MV, Patel, RS, Fairhurst-Hunter, Z, Lyall, DM, Hartwig, FP, Horta, BL, Hypponen, E, Power, C, Moldovan, M, van Iperen, E, Hovingh, GK, Demuth, I, Norman, K, Steinhagen-Thiessen, E, Demuth, J, Bertram, L, Liu, T, Coassin, S, Willeit, J, Kiechl, S, Willeit, K, Mason, D, Wright, J, Morris, R, Wanamethee, G, Whincup, P, Ben-Shlomo, Y, McLachlan, S, Price, JF, Kivimaki, M, Welch, C, Sanchez-Galvez, A, Marques-Vidal, P, Nicolaides, A, Panayiotou, AG, Onland-Moret, NC, van der Schouw, YT, Matullo, G, Fiorito, G, Guarrera, S, Sacerdote, C, Wareham, NJ, Langenberg, C, Scott, R, Luan, JA, Bobak, M, Malyutina, SA, Pajak, A, Kubinova, R, Tamosiunas, A, Pikhart, H, Husemoen, LLN, Grarup, N, Pedersen, O, Hansen, T, Linneberg, A, Simonsen, KS, Cooper, J, Humphries, SE, Brilliant, M, Kitchner, T, Hakonarson, H, Carrell, DS, McCarty, CA, Kirchner, HL, Larson, EB, Crosslin, DR, de Andrade, M, Roden, DM, Denny, JC, Carty, C, Hancock, S, Attia, J, Holliday, E, Donnell, MO, Yusuf, S, Chong, M, Pare, G, van der Harst, P, Said, MA, Eppinga, RN, Verweij, N, Snieder, H, Christen, T, Mook-Kanamori, DO, Gustafsson, S, Lind, L, Ingelsson, E, Pazoki, Raha, Franco Duran, OH, Hofman, Bert, Uitterlinden, André, Dehghan, Abbas, Teumer, A, Baumeister, S, Dorr, M, Lerch, MM, Volker, U, Volzke, H, Ward, J, Pell, JP, Smith, Derek, Meade, T, Zee, AH, Baranova, EV, Young, R, Ford, I, Campbell, A (Archie), Padmanabhan, S, Bots, ML, Grobbee, DE, Froguel, P, Thuillier, D, Balkau, B, Bonnefond, A, Cariou, B, Smart, M, Bao, Y, Kumari, M, Mahajan, A, Ridker, PM, Chasman, DI, Reiner, AP, Lange, LA, Ritchie, MD, Asselbergs, FW, Casas, JP, Keating, BJ, Preiss, D, Hingorani, AD, and Sattar, N
- Published
- 2017
13. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- Author
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Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, Fox, CS, Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, and Fox, CS
- Abstract
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
- Published
- 2016
14. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- Author
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Postmus, I, Warren, HR, Trompet, S, Arsenault, BJ, Avery, CL, Bis, JC, Chasman, DI, de Keyser, Toke, Deshmukh, HA, Evans, DS, Feng, Q, Li, X, Smit, RAJ, Smith, AV, Sun, F, Taylor, KD, Arnold, AM, Barnes, MR, Barratt, BJ, Betteridge, J, Boekholdt, SM, Boerwinkle, E, Buckley, BM, Chen, YDI, de Craen, AJM, Cummings, SR, Denny, JC, Dube, MP, Durrington, PN, Eiriksdottir, G, Ford, I, Guo, X, Harris, TB, Heckbert, SR, Hofman, Bert, Hovingh, GK, Kastelein, JJP, Launer, LJ, Liu, C-T, Liu, Y, Lumley, T, Mckeigue, PM, Munroe, PB, Neil, A, Nickerson, DA, Nyberg, F, O'Brien, E, O'Donnell, CJ, Post, W, Poulter, N, Vasan, RS, Rice, K, Rich, SS, Rivadeneira, Fernando, Sattar, N, Sever, P, Shaw-Hawkins, S, Shields, DC, Slagboom, PE (Eline), Smith, NL, Smith, JD, Sotoodehnia, N, Stanton, A, Stott, DJ, Stricker, Bruno, Sturmer, T, Uitterlinden, André, Wei, W-Q, Westendorp, RGJ, Whitsel, EA, Wiggins, KL, Wilke, RA, Ballantyne, CM, Colhoun, HM, Cupples, LA, Franco Duran, OH, Gudnason, V, Hitman, G, Palmer, CNA, Psaty, BM, Ridker, PM, Stafford, JM, Stein, CM, Tardif, J-C, Caulfield, MJ, Jukema, JW, Rotter, JI, Krauss, RM, Postmus, I, Warren, HR, Trompet, S, Arsenault, BJ, Avery, CL, Bis, JC, Chasman, DI, de Keyser, Toke, Deshmukh, HA, Evans, DS, Feng, Q, Li, X, Smit, RAJ, Smith, AV, Sun, F, Taylor, KD, Arnold, AM, Barnes, MR, Barratt, BJ, Betteridge, J, Boekholdt, SM, Boerwinkle, E, Buckley, BM, Chen, YDI, de Craen, AJM, Cummings, SR, Denny, JC, Dube, MP, Durrington, PN, Eiriksdottir, G, Ford, I, Guo, X, Harris, TB, Heckbert, SR, Hofman, Bert, Hovingh, GK, Kastelein, JJP, Launer, LJ, Liu, C-T, Liu, Y, Lumley, T, Mckeigue, PM, Munroe, PB, Neil, A, Nickerson, DA, Nyberg, F, O'Brien, E, O'Donnell, CJ, Post, W, Poulter, N, Vasan, RS, Rice, K, Rich, SS, Rivadeneira, Fernando, Sattar, N, Sever, P, Shaw-Hawkins, S, Shields, DC, Slagboom, PE (Eline), Smith, NL, Smith, JD, Sotoodehnia, N, Stanton, A, Stott, DJ, Stricker, Bruno, Sturmer, T, Uitterlinden, André, Wei, W-Q, Westendorp, RGJ, Whitsel, EA, Wiggins, KL, Wilke, RA, Ballantyne, CM, Colhoun, HM, Cupples, LA, Franco Duran, OH, Gudnason, V, Hitman, G, Palmer, CNA, Psaty, BM, Ridker, PM, Stafford, JM, Stein, CM, Tardif, J-C, Caulfield, MJ, Jukema, JW, Rotter, JI, and Krauss, RM
- Published
- 2016
15. Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network
- Author
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Bush, WS, primary, Crosslin, DR, additional, Owusu‐Obeng, A, additional, Wallace, J, additional, Almoguera, B, additional, Basford, MA, additional, Bielinski, SJ, additional, Carrell, DS, additional, Connolly, JJ, additional, Crawford, D, additional, Doheny, KF, additional, Gallego, CJ, additional, Gordon, AS, additional, Keating, B, additional, Kirby, J, additional, Kitchner, T, additional, Manzi, S, additional, Mejia, AR, additional, Pan, V, additional, Perry, CL, additional, Peterson, JF, additional, Prows, CA, additional, Ralston, J, additional, Scott, SA, additional, Scrol, A, additional, Smith, M, additional, Stallings, SC, additional, Veldhuizen, T, additional, Wolf, W, additional, Volpi, S, additional, Wiley, K, additional, Li, R, additional, Manolio, T, additional, Bottinger, E, additional, Brilliant, MH, additional, Carey, D, additional, Chisholm, RL, additional, Chute, CG, additional, Haines, JL, additional, Hakonarson, H, additional, Harley, JB, additional, Holm, IA, additional, Kullo, IJ, additional, Jarvik, GP, additional, Larson, EB, additional, McCarty, CA, additional, Williams, MS, additional, Denny, JC, additional, Rasmussen‐Torvik, LJ, additional, Roden, DM, additional, and Ritchie, MD, additional
- Published
- 2016
- Full Text
- View/download PDF
16. Physician response to implementation of genotype‐tailored antiplatelet therapy
- Author
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Peterson, JF, primary, Field, JR, additional, Unertl, KM, additional, Schildcrout, JS, additional, Johnson, DC, additional, Shi, Y, additional, Danciu, I, additional, Cleator, JH, additional, Pulley, JM, additional, McPherson, JA, additional, Denny, JC, additional, Laposata, M, additional, Roden, DM, additional, and Johnson, KB, additional
- Published
- 2016
- Full Text
- View/download PDF
17. Integrating electronic health record genotype and phenotype datasets to transform patient care
- Author
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Roden, DM, primary and Denny, JC, additional
- Published
- 2016
- Full Text
- View/download PDF
18. Biological interpretation of genome-wide association studies using predicted gene functions
- Author
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Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, A, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, de Groot, L, Groves, C, Haessler, J, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, van Dijk, S, van Schoor, N, van der Velde, N, van Heemst, D, van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, I, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, de Faire, U, den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Chu AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Mägi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AA, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Mateo Leach I, Medina Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Ärnlöv J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blüher M, Bolton JL, Böttcher Y, Boyd HA, Bruinenberg M, Buckley BM, Buyske S, Caspersen IH, Chines PS, Clarke R, Claudi Boehm S, Cooper M, Daw EW, De Jong A, Deelen J, Delgado G, Denny JC, Dhonukshe Rutten R, Dimitriou M, Doney AS, Dörr M, Eklund N, Eury E, Folkersen L, Garcia ME, Geller F, Giedraitis V, Go AS, Grallert H, Grammer TB, Gräßler J, Grönberg H, de Groot LC, Groves CJ, Haessler J, Haller T, Hallmans G, Hannemann A, Hartman CA, Hassinen M, Hayward C, Heard Costa NL, Helmer Q, Hemani G, Henders AK, Hillege HL, Hlatky MA, Hoffmann W, Hoffmann P, Holmen O, Houwing Duistermaat JJ, Illig T, Isaacs A, James AL, Jeff J, Johansen B, Johansson Å, Jolley J, Juliusdottir T, Junttila J, Kho AN, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Lindström J, Lobbens S, Lorentzon M, Lu Y, Lyssenko V, Magnusson PK, Mahajan A, Maillard M, McArdle WL, McKenzie CA, McLachlan S, McLaren PJ, Menni C, Merger S, Milani L, Moayyeri A, Monda KL, Morken MA, Müller G, Müller Nurasyid M, Musk AW, Narisu N, Nauck M, Nolte IM, Nöthen MM, Oozageer L, Pilz S, Rayner NW, Renstrom F, Robertson NR, Rose LM, Roussel R, Sanna S, Scharnagl H, Scholtens S, Schumacher FR, Schunkert H, Scott RA, Sehmi J, Seufferlein T, Shi J, Silventoinen K, Smit JH, Smith AV, Smolonska J, Stanton AV, Stirrups K, Stott DJ, Stringham HM, Sundström J, Swertz MA, Syvänen AC, Tayo BO, Thorleifsson G, Tyrer JP, van Dijk S, van Schoor NM, van der Velde N, van Heemst D, van Oort FV, Vermeulen SH, Verweij N, Vonk JM, Waite LL, Waldenberger M, Wennauer R, Wilkens LR, Willenborg C, Wilsgaard T, Wojczynski MK, Wong A, Wright AF, Zhang Q, Arveiler D, Bakker SJ, Beilby J, Bergman RN, Bergmann S, Biffar R, Blangero J, Boomsma I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, Brown MJ, Campbell H, Caulfield MJ, Chakravarti A, Collins R, Collins FS, Crawford DC, Cupples LA, Danesh J, de Faire U, den Ruijter HM, Erbel R, Erdmann J, Eriksson JG, Farrall M, Ferrannini E, Ferrières J, Ford I, Forouhi NG, Forrester T, Gansevoort RT, Gejman PV, Gieger C, Golay A, Gottesman O, Gudnason V, Gyllensten U, Haas DW, Hall AS, Harris TB, Hattersley AT, Heath AC, Hengstenberg C, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Hovingh GK, Humphries SE, Hunt SC, Hypponen E, Jacobs KB, Jarvelin MR, Jousilahti P, Jula AM, Kaprio J, Kastelein JJ, Kayser M, Kee F, Keinanen Kiukaanniemi SM, Kiemeney LA, Kooner JS, Kooperberg C, Koskinen S, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Le Marchand L, Lehtimäki T, Lupoli S, Madden PA, Männistö S, Manunta P, Marette A, Matise TC, McKnight B, Meitinger T, Moll FL, Montgomery GW, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Ouwehand WH, Pasterkamp G, Peters A, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ritchie M, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schwarz PE, Sebert S, Sever P, Shuldiner AR, Sinisalo J, Steinthorsdottir V, Stolk RP, Tardif JC, Tönjes A, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PI, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hayes MG, Hui J, Hunter DJ, Hveem K, Jukema JW, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, März W, Melbye M, Moebus S, Munroe PB, Njølstad I, Oostra BA, Palmer CN, Pedersen NL, Perola M, Pérusse L, Peters U, Powell JE, Power C, Quertermous T, Rauramaa R, Reinmaa E, Ridker PM, Rivadeneira F, Rotter JI, Saaristo TE, Saleheen D, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Strauch K, Stumvoll M, Tuomilehto J, Uusitupa M, van der Harst P, Völzke H, Walker M, Wareham NJ, Watkins H, Wichmann HE, Wilson JF, Zanen P, Deloukas P, Heid IM, Lindgren CM, Mohlke KL, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, Frayling T.M., Pers, T, Karjalainen, J, Chan, Y, Westra, H, Wood, A, Yang, J, Lui, J, Vedantam, S, Gustafsson, S, Esko, T, Frayling, T, Speliotes, E, Boehnke, M, Raychaudhuri, S, Fehrmann, R, Hirschhorn, J, Franke, L, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Ferreira, T, Jackson, A, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, E, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, A, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, de Groot, L, Groves, C, Haessler, J, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, van Dijk, S, van Schoor, N, van der Velde, N, van Heemst, D, van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, I, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, de Faire, U, den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, van Duijn, C, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L, Chu AY, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich ML, Croteau Chonka DC, Day FR, Duan Y, Fall T, Fehrmann R, Ferreira T, Jackson AU, Karjalainen J, Lo KS, Locke AE, Mägi R, Mihailov E, Porcu E, Randall JC, Scherag A, Vinkhuyzen AA, Winkler TW, Workalemahu T, Zhao JH, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Fraser RM, Goel A, Gong J, Justice E, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Mateo Leach I, Medina Gomez C, Nalls MA, Nyholt DR, Palmer CD, Pasko D, Pechlivanis S, Prokopenko I, Ried JS, Ripke S, Shungin D, Stancáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Afzal U, Ärnlöv J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blüher M, Bolton JL, Böttcher Y, Boyd HA, Bruinenberg M, Buckley BM, Buyske S, Caspersen IH, Chines PS, Clarke R, Claudi Boehm S, Cooper M, Daw EW, De Jong A, Deelen J, Delgado G, Denny JC, Dhonukshe Rutten R, Dimitriou M, Doney AS, Dörr M, Eklund N, Eury E, Folkersen L, Garcia ME, Geller F, Giedraitis V, Go AS, Grallert H, Grammer TB, Gräßler J, Grönberg H, de Groot LC, Groves CJ, Haessler J, Haller T, Hallmans G, Hannemann A, Hartman CA, Hassinen M, Hayward C, Heard Costa NL, Helmer Q, Hemani G, Henders AK, Hillege HL, Hlatky MA, Hoffmann W, Hoffmann P, Holmen O, Houwing Duistermaat JJ, Illig T, Isaacs A, James AL, Jeff J, Johansen B, Johansson Å, Jolley J, Juliusdottir T, Junttila J, Kho AN, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Lindström J, Lobbens S, Lorentzon M, Lu Y, Lyssenko V, Magnusson PK, Mahajan A, Maillard M, McArdle WL, McKenzie CA, McLachlan S, McLaren PJ, Menni C, Merger S, Milani L, Moayyeri A, Monda KL, Morken MA, Müller G, Müller Nurasyid M, Musk AW, Narisu N, Nauck M, Nolte IM, Nöthen MM, Oozageer L, Pilz S, Rayner NW, Renstrom F, Robertson NR, Rose LM, Roussel R, Sanna S, Scharnagl H, Scholtens S, Schumacher FR, Schunkert H, Scott RA, Sehmi J, Seufferlein T, Shi J, Silventoinen K, Smit JH, Smith AV, Smolonska J, Stanton AV, Stirrups K, Stott DJ, Stringham HM, Sundström J, Swertz MA, Syvänen AC, Tayo BO, Thorleifsson G, Tyrer JP, van Dijk S, van Schoor NM, van der Velde N, van Heemst D, van Oort FV, Vermeulen SH, Verweij N, Vonk JM, Waite LL, Waldenberger M, Wennauer R, Wilkens LR, Willenborg C, Wilsgaard T, Wojczynski MK, Wong A, Wright AF, Zhang Q, Arveiler D, Bakker SJ, Beilby J, Bergman RN, Bergmann S, Biffar R, Blangero J, Boomsma I, Bornstein SR, Bovet P, BRAMBILLA, PAOLO, Brown MJ, Campbell H, Caulfield MJ, Chakravarti A, Collins R, Collins FS, Crawford DC, Cupples LA, Danesh J, de Faire U, den Ruijter HM, Erbel R, Erdmann J, Eriksson JG, Farrall M, Ferrannini E, Ferrières J, Ford I, Forouhi NG, Forrester T, Gansevoort RT, Gejman PV, Gieger C, Golay A, Gottesman O, Gudnason V, Gyllensten U, Haas DW, Hall AS, Harris TB, Hattersley AT, Heath AC, Hengstenberg C, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Hovingh GK, Humphries SE, Hunt SC, Hypponen E, Jacobs KB, Jarvelin MR, Jousilahti P, Jula AM, Kaprio J, Kastelein JJ, Kayser M, Kee F, Keinanen Kiukaanniemi SM, Kiemeney LA, Kooner JS, Kooperberg C, Koskinen S, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Le Marchand L, Lehtimäki T, Lupoli S, Madden PA, Männistö S, Manunta P, Marette A, Matise TC, McKnight B, Meitinger T, Moll FL, Montgomery GW, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Ouwehand WH, Pasterkamp G, Peters A, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ritchie M, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schwarz PE, Sebert S, Sever P, Shuldiner AR, Sinisalo J, Steinthorsdottir V, Stolk RP, Tardif JC, Tönjes A, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PI, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hayes MG, Hui J, Hunter DJ, Hveem K, Jukema JW, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, März W, Melbye M, Moebus S, Munroe PB, Njølstad I, Oostra BA, Palmer CN, Pedersen NL, Perola M, Pérusse L, Peters U, Powell JE, Power C, Quertermous T, Rauramaa R, Reinmaa E, Ridker PM, Rivadeneira F, Rotter JI, Saaristo TE, Saleheen D, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Strauch K, Stumvoll M, Tuomilehto J, Uusitupa M, van der Harst P, Völzke H, Walker M, Wareham NJ, Watkins H, Wichmann HE, Wilson JF, Zanen P, Deloukas P, Heid IM, Lindgren CM, Mohlke KL, Thorsteinsdottir U, Barroso I, Fox CS, North KE, Strachan DP, Beckmann JS, Berndt SI, Borecki IB, McCarthy MI, Metspalu A, Stefansson K, Uitterlinden AG, van Duijn CM, Willer CJ, Price AL, Lettre G, Loos RJ, Weedon MN, Ingelsson E, O'Connell JR, Abecasis GR, Chasman DI, Goddard ME, Visscher PM, and Frayling T.M.
- Abstract
The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.
- Published
- 2015
19. Defining the role of common variation in the genomic and biological architecture of adult human height.
- Author
-
Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., Frayling, T.M., Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., and Frayling, T.M.
- Abstract
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
20. Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene
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Okada, Y, Diogo, D, Greenberg, JD, Mouassess, F, Achkar, WAL, Fulton, RS, Denny, JC, Gupta, N, Mirel, D, Gabriel, S, Li, G, Kremer, JM, Pappas, DA, Carroll, RJ, Eyler, AE, Trynka, G, Stahl, EA, Cui, J, Saxena, R, Coenen, MJH, Guchelaar, HJ, Huizinga, TWJ, Dieudé, P, Mariette, X, Barton, A, Canhão, H, Fonseca, JE, De Vries, N, Tak, PP, Moreland, LW, Bridges, SL, Miceli-Richard, C, Choi, HK, Kamatani, Y, Galan, P, Lathrop, M, Raj, T, De Jager, PL, Raychaudhuri, S, Worthington, J, Padyukov, L, Klareskog, L, Siminovitch, KA, Gregersen, PK, Mardis, ER, Arayssi, T, Kazkaz, LA, Plenge, RM, Okada, Y, Diogo, D, Greenberg, JD, Mouassess, F, Achkar, WAL, Fulton, RS, Denny, JC, Gupta, N, Mirel, D, Gabriel, S, Li, G, Kremer, JM, Pappas, DA, Carroll, RJ, Eyler, AE, Trynka, G, Stahl, EA, Cui, J, Saxena, R, Coenen, MJH, Guchelaar, HJ, Huizinga, TWJ, Dieudé, P, Mariette, X, Barton, A, Canhão, H, Fonseca, JE, De Vries, N, Tak, PP, Moreland, LW, Bridges, SL, Miceli-Richard, C, Choi, HK, Kamatani, Y, Galan, P, Lathrop, M, Raj, T, De Jager, PL, Raychaudhuri, S, Worthington, J, Padyukov, L, Klareskog, L, Siminovitch, KA, Gregersen, PK, Mardis, ER, Arayssi, T, Kazkaz, LA, and Plenge, RM
- Abstract
Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al.
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- 2014
21. Characterization of statin dose response in electronic medical records.
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Wei, W-Q, Wei, W-Q, Feng, Q, Jiang, L, Waitara, MS, Iwuchukwu, OF, Roden, DM, Jiang, M, Xu, H, Krauss, RM, Rotter, JI, Nickerson, DA, Davis, RL, Berg, RL, Peissig, PL, McCarty, CA, Wilke, RA, Denny, JC, Wei, W-Q, Wei, W-Q, Feng, Q, Jiang, L, Waitara, MS, Iwuchukwu, OF, Roden, DM, Jiang, M, Xu, H, Krauss, RM, Rotter, JI, Nickerson, DA, Davis, RL, Berg, RL, Peissig, PL, McCarty, CA, Wilke, RA, and Denny, JC
- Abstract
Efforts to define the genetic architecture underlying variable statin response have met with limited success, possibly because previous studies were limited to effect based on a single dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in subjects homozygous for the minor allele vs. 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand the genetic factors contributing to drug response.
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- 2014
22. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
- Author
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Postmus, I, Trompet, S, Deshmukh, HA, Barnes, MR, Li, XH, Warren, HR, Chasman, DI, Zhou, KX, Arsenault, BJ, Donnelly, LA, Wiggins, KL, Avery, CL, Griffin, P, Feng, QP, Taylor, KD, Li, G, Evans, DS, Smith, AV, de Keyser, Toke, Johnson, AD, de Craen, AJM, Stott, DJ, Buckley, BM, Ford, I, Westendorp, RGJ, Slagboom, PE (Eline), Sattar, N, Munroe, PB, Sever, P, Poulter, N, Stanton, A, Shields, DC, O'Brien, E, Shaw-Hawkins, S, Chen, YDI, Nickerson, DA, Smith, JD, Dube, MP, Boekholdt, SM, Hovingh, GK, Kastelein, JJP, Mckeigue, PM, Betteridge, J, Neil, A, Durrington, PN, Doney, A, Carr, F, Morris, A, McCarthy, MI, Groop, L, Ahlqvist, E, Bis, JC, Rice, K, Smith, NL, Lumley, T, Whitsel, EA, Sturmer, T, Boerwinkle, E, Ngwa, JS, O'Donnell, CJ, Vasan, RS, Wei, WQ, Wilke, RA, Liu, CT, Sun, FG, Guo, XQ, Heckbert, SR, Post, W, Sotoodehnia, N, Arnold, AM, Stafford, JM, Ding, JZ (Jing Zhong), Herrington, DM, Kritchevsky, SB, Eiriksdottir, G, Launer, LJ (Lenore), Harris, TB, Chu, AY, Giulianini, F, MacFadyen, JG, Barratt, BJ, Nyberg, F, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Emilsson, V, Franco Duran, OH, Ridker, PM, Gudnason, V, Liu, YM, Denny, JC, Ballantyne, CM, Rotter, JI, Cupples, LA, Psaty, BM, Palmer, CNA, Tardif, JC, Colhoun, HM, Hitman, G, Krauss, RM, Jukema, JW, Caulfield, MJ, Postmus, I, Trompet, S, Deshmukh, HA, Barnes, MR, Li, XH, Warren, HR, Chasman, DI, Zhou, KX, Arsenault, BJ, Donnelly, LA, Wiggins, KL, Avery, CL, Griffin, P, Feng, QP, Taylor, KD, Li, G, Evans, DS, Smith, AV, de Keyser, Toke, Johnson, AD, de Craen, AJM, Stott, DJ, Buckley, BM, Ford, I, Westendorp, RGJ, Slagboom, PE (Eline), Sattar, N, Munroe, PB, Sever, P, Poulter, N, Stanton, A, Shields, DC, O'Brien, E, Shaw-Hawkins, S, Chen, YDI, Nickerson, DA, Smith, JD, Dube, MP, Boekholdt, SM, Hovingh, GK, Kastelein, JJP, Mckeigue, PM, Betteridge, J, Neil, A, Durrington, PN, Doney, A, Carr, F, Morris, A, McCarthy, MI, Groop, L, Ahlqvist, E, Bis, JC, Rice, K, Smith, NL, Lumley, T, Whitsel, EA, Sturmer, T, Boerwinkle, E, Ngwa, JS, O'Donnell, CJ, Vasan, RS, Wei, WQ, Wilke, RA, Liu, CT, Sun, FG, Guo, XQ, Heckbert, SR, Post, W, Sotoodehnia, N, Arnold, AM, Stafford, JM, Ding, JZ (Jing Zhong), Herrington, DM, Kritchevsky, SB, Eiriksdottir, G, Launer, LJ (Lenore), Harris, TB, Chu, AY, Giulianini, F, MacFadyen, JG, Barratt, BJ, Nyberg, F, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, Rivadeneira, Fernando, Emilsson, V, Franco Duran, OH, Ridker, PM, Gudnason, V, Liu, YM, Denny, JC, Ballantyne, CM, Rotter, JI, Cupples, LA, Psaty, BM, Palmer, CNA, Tardif, JC, Colhoun, HM, Hitman, G, Krauss, RM, Jukema, JW, and Caulfield, MJ
- Abstract
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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- 2014
23. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- Author
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Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, de Bakker, PI, Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, and de Bakker, PI
- Abstract
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
- Published
- 2014
24. Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing
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Van Driest, SL, primary, Shi, Y, additional, Bowton, EA, additional, Schildcrout, JS, additional, Peterson, JF, additional, Pulley, J, additional, Denny, JC, additional, and Roden, DM, additional
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- 2013
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25. Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing.
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Van Driest, SL, Shi, Y, Bowton, EA, Schildcrout, JS, Peterson, JF, Pulley, J, Denny, JC, and Roden, DM
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PHARMACOGENOMICS ,GENETIC databases ,GENE frequency ,DRUG interactions ,ELECTRONIC health records ,GENETIC testing - Abstract
Since September 2010, more than 10,000 patients have undergone preemptive, panel-based pharmacogenomic testing through the Vanderbilt Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment program. Analysis of the genetic data from the first 9,589 individuals reveals that the frequency of genetic variants is concordant with published allele frequencies. Based on five currently implemented drug-gene interactions, the multiplexed test identified one or more actionable variants in 91% of the genotyped patients and in 96% of African American patients. Using medication exposure data from electronic medical records, we compared a theoretical 'reactive,' prescription-triggered, serial single-gene testing strategy with our preemptive, multiplexed genotyping approach. Reactive genotyping would have generated 14,656 genetic tests. These data highlight three advantages of preemptive genotyping: (i) the vast majority of patients carry at least one pharmacogenetic variant; (ii) data are available at the point of care; and (iii) there is a substantial reduction in testing burden compared with a reactive strategy. [ABSTRACT FROM AUTHOR]
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- 2014
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26. Applying semantic-based probabilistic context-free grammar to medical language processing--a preliminary study on parsing medication sentences.
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Xu H, Abdelrahman S, Lu Y, Denny JC, Doan S, Xu, Hua, AbdelRahman, Samir, Lu, Yanxin, Denny, Joshua C, and Doan, Son
- Abstract
Semantic-based sublanguage grammars have been shown to be an efficient method for medical language processing. However, given the complexity of the medical domain, parsers using such grammars inevitably encounter ambiguous sentences, which could be interpreted by different groups of production rules and consequently result in two or more parse trees. One possible solution, which has not been extensively explored previously, is to augment productions in medical sublanguage grammars with probabilities to resolve the ambiguity. In this study, we associated probabilities with production rules in a semantic-based grammar for medication findings and evaluated its performance on reducing parsing ambiguity. Using the existing data set from 2009 i2b2 NLP (Natural Language Processing) challenge for medication extraction, we developed a semantic-based CFG (Context Free Grammar) for parsing medication sentences and manually created a Treebank of 4564 medication sentences from discharge summaries. Using the Treebank, we derived a semantic-based PCFG (Probabilistic Context Free Grammar) for parsing medication sentences. Our evaluation using a 10-fold cross validation showed that the PCFG parser dramatically improved parsing performance when compared to the CFG parser. [ABSTRACT FROM AUTHOR]
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- 2011
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27. Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science.
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Denny JC, Ritchie MD, Crawford DC, Schildcrout JS, Ramirez AH, Pulley JM, Basford MA, Masys DR, Haines JL, Roden DM, Denny, Joshua C, Ritchie, Marylyn D, Crawford, Dana C, Schildcrout, Jonathan S, Ramirez, Andrea H, Pulley, Jill M, Basford, Melissa A, Masys, Daniel R, Haines, Jonathan L, and Roden, Dan M
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- 2010
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28. Tracking medical students' clinical experiences using natural language processing.
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Denny JC, Bastarache L, Sastre EA, Spickard A 3rd, Denny, Joshua C, Bastarache, Lisa, Sastre, Elizabeth Ann, and Spickard, Anderson 3rd
- Abstract
Graduate medical students must demonstrate competency in clinical skills. Current tracking methods rely either on manual efforts or on simple electronic entry to record clinical experience. We evaluated automated methods to locate 10 institution-defined core clinical problems from three medical students' clinical notes (n=290). Each note was processed with section header identification algorithms and the KnowledgeMap concept identifier to locate Unified Medical Language System (UMLS) concepts. The best performing automated search strategies accurately classified documents containing primary discussions to the core clinical problems with area under receiver operator characteristic curve of 0.90-0.94. Recall and precision for UMLS concept identification was 0.91 and 0.92, respectively. Of the individual note section, concepts found within the chief complaint, history of present illness, and assessment and plan were the strongest predictors of relevance. This automated method of tracking can provide detailed, pertinent reports of clinical experience that does not require additional work from medical trainees. The coupling of section header identification and concept identification holds promise for other natural language processing tasks, such as clinical research or phenotype identification. [ABSTRACT FROM AUTHOR]
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- 2009
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29. 'Understanding' medical school curriculum content using KnowledgeMap.
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Denny JC, Smithers JD, Miller RA, and Spickard A III
- Abstract
OBJECTIVE: To describe the development and evaluation of computational tools to identify concepts within medical curricular documents, using information derived from the National Library of Medicine's Unified Medical Language System (UMLS). The long-term goal of the KnowledgeMap (KM) project is to provide faculty and students with an improved ability to develop, review, and integrate components of the medical school curriculum. DESIGN: The KM concept identifier uses lexical resources partially derived from the UMLS (SPECIALIST lexicon and Metathesaurus), heuristic language processing techniques, and an empirical scoring algorithm. KM differentiates among potentially matching Metathesaurus concepts within a source document. The authors manually identified important 'gold standard' biomedical concepts within selected medical school full-content lecture documents and used these documents to compare KM concept recognition with that of a known state-of-the-art 'standard'-the National Library of Medicine's MetaMap program. MEASUREMENTS: The number of 'gold standard' concepts in each lecture document identified by either KM or MetaMap, and the cause of each failure or relative success in a random subset of documents. RESULTS: For 4,281 'gold standard' concepts, MetaMap matched 78% and KM 82%. Precision for 'gold standard' concepts was 85% for MetaMap and 89% for KM. The heuristics of KM accurately matched acronyms, concepts underspecified in the document, and ambiguous matches. The most frequent cause of matching failures was absence of target concepts from the UMLS Metathesaurus. CONCLUSION: The prototypic KM system provided an encouraging rate of concept extraction for representative medical curricular texts. Future versions of KM should be evaluated for their ability to allow administrators, lecturers, and students to navigate through the medical curriculum to locate redundancies, find interrelated information, and identify omissions. In addition, the ability of KM to meet specific, personal information needs should be assessed. [ABSTRACT FROM AUTHOR]
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- 2003
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30. Portability of an algorithm to identify rheumatoid arthritis in electronic health records.
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Carroll RJ, Thompson WK, Eyler AE, Mandelin AM, Cai T, Zink RM, Pacheco JA, Boomershine CS, Lasko TA, Xu H, Karlson EW, Perez RG, Gainer VS, Murphy SN, Ruderman EM, Pope RM, Plenge RM, Kho AN, Liao KP, and Denny JC
- Abstract
Objectives: Electronic health records (EHR) can allow for the generation of large cohorts of individuals with given diseases for clinical and genomic research. A rate-limiting step is the development of electronic phenotype selection algorithms to find such cohorts. This study evaluated the portability of a published phenotype algorithm to identify rheumatoid arthritis (RA) patients from EHR records at three institutions with different EHR systems.Materials and Methods: Physicians reviewed charts from three institutions to identify patients with RA. Each institution compiled attributes from various sources in the EHR, including codified data and clinical narratives, which were searched using one of two natural language processing (NLP) systems. The performance of the published model was compared with locally retrained models.Results: Applying the previously published model from Partners Healthcare to datasets from Northwestern and Vanderbilt Universities, the area under the receiver operating characteristic curve was found to be 92% for Northwestern and 95% for Vanderbilt, compared with 97% at Partners. Retraining the model improved the average sensitivity at a specificity of 97% to 72% from the original 65%. Both the original logistic regression models and locally retrained models were superior to simple billing code count thresholds.Discussion: These results show that a previously published algorithm for RA is portable to two external hospitals using different EHR systems, different NLP systems, and different target NLP vocabularies. Retraining the algorithm primarily increased the sensitivity at each site.Conclusion: Electronic phenotype algorithms allow rapid identification of case populations in multiple sites with little retraining. [ABSTRACT FROM AUTHOR]- Published
- 2012
31. PheWAS analysis on large-scale biobank data with PheTK.
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Tran TC, Schlueter DJ, Zeng C, Mo H, Carroll RJ, and Denny JC
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- Humans, Electronic Health Records, Phenotype, Genome-Wide Association Study methods, Phenomics methods, Databases, Genetic, Biological Specimen Banks, Software
- Abstract
Summary: With the rapid growth of genetic data linked to electronic health record (EHR) data in huge cohorts, large-scale phenome-wide association study (PheWAS) have become powerful discovery tools in biomedical research. PheWAS is an analysis method to study phenotype associations utilizing longitudinal EHR data. Previous PheWAS packages were developed mostly with smaller datasets and with earlier PheWAS approaches. PheTK was designed to simplify analysis and efficiently handle biobank-scale data. PheTK uses multithreading and supports a full PheWAS workflow including extraction of data from OMOP databases and Hail matrix tables as well as PheWAS analysis for both phecode version 1.2 and phecodeX. Benchmarking results showed PheTK took 64% less time than the R PheWAS package to complete the same workflow. PheTK can be run locally or on cloud platforms such as the All of Us Researcher Workbench (All of Us) or the UK Biobank (UKB) Research Analysis Platform (RAP)., Availability and Implementation: The PheTK package is freely available on the Python Package Index, on GitHub under GNU General Public License (GPL-3) at https://github.com/nhgritctran/PheTK, and on Zenodo, DOI 10.5281/zenodo.14217954, at https://doi.org/10.5281/zenodo.14217954. PheTK is implemented in Python and platform independent., (Published by Oxford University Press 2024.)
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- 2024
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32. A One-Shot Lossless Algorithm for Cross-Cohort Learning in Mixed-Outcomes Analysis.
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Li R, Benz L, Duan R, Denny JC, Hakonarson H, Mosley JD, Smoller JW, Wei WQ, Lumley T, Ritchie MD, Moore JH, and Chen Y
- Abstract
In cross-cohort studies, integrating diverse datasets, such as electronic health records (EHRs), is both essential and challenging due to cohort-specific variations, distributed data storage, and data privacy concerns. Traditional methods often require data pooling or complex data harmonization, which can reduce efficiency and limit the scope of cross-cohort learning. We introduce mixWAS, a one-shot, lossless algorithm that efficiently integrates distributed EHR datasets via summary statistics. Unlike existing approaches, mixWAS preserves cohort-specific covariate associations and supports simultaneous mixed-outcome analyses. Simulations demonstrate that mixWAS outperforms conventional methods in accuracy and efficiency across various scenarios. Applied to EHR data from seven cohorts in the US, mixWAS identified 4,534 significant cross-cohort genetic associations among traits such as blood lipids, BMI, and circulatory diseases. Validation with an independent UK EHR dataset confirmed 97.7% of these associations, underscoring the algorithm's robustness. By enabling lossless cross-cohort integration, mixWAS improves the precision of multi-outcome analyses and expands the potential for actionable insights in healthcare research.
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- 2024
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33. Informatics innovation to provide return of value to participant communities in the All of Us Research Program.
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Mapes BM, Peterson RS, Watson K, Basford M, Cohn E, Harris PA, and Denny JC
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- United States, Humans, Precision Medicine, Biomedical Research, Access to Information, Medical Informatics
- Abstract
Objectives: The All of Us Research Program harnesses advances in technology, science, and engagement for precision medicine research. We describe informatics innovations which support that goal and return value to the participant cohort and community., Materials and Methods: Research data from the All of Us Research Program are available to authorized users on the All of Us Researcher Workbench. We describe the technical infrastructure that enables data access and usage for researchers. Participants are considered partners. To ensure return of value, we outline participant access to information., Results: The All of Us Research Hub allows broad access to data, regardless of background. The innovations described are rooted in the program's core values: participation is open and reflects the diversity of the United States; participants are partners and have access to their information; transparency, security, and privacy are of the highest importance; data are broadly accessible; and the program promotes positive change. We assess research impact and reflect on how All of Us can increase existing return of value to participant communities through future informatics advancements., Discussion: The program will continue to support efforts to ensure equitable access to data and return of value to participants. Looking ahead, we invite the community to join us., Conclusion: All of Us research findings can change clinical care, inform guidelines, and set a new bar for data sharing. The ultimate return of value is better care for all., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)
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- 2024
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34. Racial and Ethnic Disparities in Antihypertensive Medication Prescribing Patterns and Effectiveness.
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Goleva SB, Williams A, Schlueter DJ, Keaton JM, Tran TC, Waxse BJ, Ferrara TM, Cassini T, Mo H, and Denny JC
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- Adult, Aged, Female, Humans, Male, Middle Aged, Black or African American, Blood Pressure drug effects, Ethnicity, Hispanic or Latino, Longitudinal Studies, Treatment Outcome, United States, White, Antihypertensive Agents therapeutic use, Healthcare Disparities ethnology, Hypertension drug therapy, Hypertension ethnology, Practice Patterns, Physicians' statistics & numerical data
- Abstract
Variability in drug effectiveness and provider prescribing patterns have been reported in different racial and ethnic populations. We sought to evaluate antihypertensive drug effectiveness and prescribing patterns among self-identified Hispanic/Latino (Hispanic), Non-Hispanic Black (Black), and Non-Hispanic White (White) populations that enrolled in the NIH All of Us Research Program, a US longitudinal cohort. We employed a self-controlled case study method using electronic health record and survey data from 17,718 White, Hispanic, and Black participants who were diagnosed with essential hypertension and prescribed at least one of 19 commonly used antihypertensive medications. Effectiveness was determined by calculating the reduction in systolic blood pressure measurements after 28 or more days of drug exposure. Starting systolic blood pressure and effectiveness for each medication were compared for self-reported Black, Hispanic, and White participants using adjusted linear regressions. Black and Hispanic participants were started on antihypertensive medications at significantly higher SBP than White participants in 13 and 7 out of 19 medications, respectively. More Black participants were prescribed multiple antihypertensive medications (58.46%) than White (52.35%) or Hispanic (49.9%) participants. First-line HTN medications differed by race and ethnicity. Following the 2017 American College of Cardiology and the American Heart Association High Blood Pressure Guideline release, around 64% of Black participants were prescribed a recommended first-line antihypertensive drug compared with 76% of White and 82% of Hispanic participants. Effect sizes suggested that most antihypertensive drugs were less effective in Hispanic and Black, compared with White, participants, and statistical significance was reached in 6 out of 19 drugs. These results indicate that Black and Hispanic populations may benefit from earlier intervention and screening and highlight the potential benefits of personalizing first-line medications., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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35. Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.
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Mo H, Channa Y, Ferrara TM, Waxse BJ, Schlueter DJ, Tran TC, Awan AH, Goleva SB, Williams A, Babbar A, Stubblefield O, Keaton JM, Larson EA, Wilke RA, and Denny JC
- Abstract
Selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and norepinephrine-dopamine reuptake inhibitor (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks of hyponatremia associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) and NRI (bupropion), as well as omeprazole as a reference, with a retrospective observational cohort study in the All of Us Research Program, a national multicenter research cohort containing de-identified electronic health records (EHR). Participants who had been prescribed monotherapy with any of eight common antidepressants were included, with each drug considered as a separate arm indexed with a start date. Events were defined as the first occurrence of a low plasma sodium measurement or a clinical diagnosis recorded for either hyponatremia or SIADH. Those who did not have events were censored at their last plasma sodium measurement. A total of 17,439 individuals were exposed to one of the eight antidepressants as monotherapy. The overall incidences for hyponatremia were 0.87% in the first 30 days and 10.5% in the first 3 years in the antidepressant arms. Compared to sertraline, duloxetine (hazard ratio [HR] = 1.37 [1.19-1.58]) and escitalopram (HR = 1.16 [1.01-1.33]) were associated with the highest overall risk of hyponatremia, and bupropion (HR = 0.83 [0.73-0.94]) and paroxetine (HR = 0.78 [0.65-0.93]) were associated with the lowest risk. The risks were unchanged after adjusting for comorbidity and polypharmacy. Such information could help guide providers in managing patients and their risks of hyponatremia when on common antidepressants., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2024
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36. Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.
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Ritchie SC, Taylor HJ, Liang Y, Manikpurage HD, Pennells L, Foguet C, Abraham G, Gibson JT, Jiang X, Liu Y, Xu Y, Kim LG, Mahajan A, McCarthy MI, Kaptoge S, Lambert SA, Wood A, Sim X, Collins FS, Denny JC, Danesh J, Butterworth AS, Di Angelantonio E, and Inouye M
- Abstract
Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score., Competing Interests: Competing Interests During the course of this project G.A. became a full-time employee of CSL Ltd. All significant contributions to this study were made prior to this role and CSL Ltd had no input to the study. A.M. and M.I.M are both employees of Genentech Ltd, and holders of Roche stock. Genentech Ltd was not involved with the described work. J.D. serves on scientific advisory boards for AstraZeneca, Novartis, and UK Biobank, and has received multiple grants from academic, charitable and industry sources outside of the submitted work. A.S.B. reports institutional grants from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Novartis, Regeneron and Sanofi. M.I. is a trustee of the Public Health Genomics (PHG) Foundation, a member of the Scientific Advisory Board of Open Targets, and has research collaborations with AstraZeneca, Nightingale Health and Pfizer which are unrelated to this study. The remaining authors declare no competing interests.
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- 2024
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37. Phenome-Wide Association of APOE Alleles in the All of Us Research Program.
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Khajouei E, Ghisays V, Piras IS, Martinez KL, Naymik M, Ngo P, Tran TC, Denny JC, Wheeler TJ, Huentelman MJ, Reiman EM, and Karnes JH
- Abstract
Background: Genetic variation in APOE is associated with altered lipid metabolism, as well as cardiovascular and neurodegenerative disease risk. However, prior studies are largely limited to European ancestry populations and differential risk by sex and ancestry has not been widely evaluated. We utilized a phenome-wide association study (PheWAS) approach to explore APOE -associated phenotypes in the All of Us Research Program., Methods: We determined APOE alleles for 181,880 All of Us participants with whole genome sequencing and electronic health record (EHR) data, representing seven gnomAD ancestry groups. We tested association of APOE variants, ordered based on Alzheimer's disease risk hierarchy (ε2/ε2<ε2/ε3<ε3/ε3<ε2/ε4<ε3/ε4<ε4/ε4), with 2,318 EHR-derived phenotypes. Bonferroni-adjusted analyses were performed overall, by ancestry, by sex, and with adjustment for social determinants of health (SDOH)., Findings: In the overall cohort, PheWAS identified 17 significant associations, including an increased odds of hyperlipidemia (OR 1.15 [1.14-1.16] per APOE genotype group; P =1.8×10
-129 ), dementia, and Alzheimer's disease (OR 1.55 [1.40-1.70]; P =5×10-19 ), and a reduced odds of fatty liver disease (OR 0.93 [0.90-0.95]; P =1.6×10-9 ) and chronic liver disease. ORs were similar after SDOH adjustment and by sex, except for an increased number of cardiovascular associations in males, and decreased odds of noninflammatory disorders of vulva and perineum in females (OR 0.89 [0.84-0.94]; P =1.1×10-5 ). Significant heterogeneity was observed for hyperlipidemia and mild cognitive impairment across ancestry. Unique associations by ancestry included transient retinal arterial occlusion in the European ancestry group, and first-degree atrioventricular block in the American Admixed/Latino ancestry group., Interpretation: We replicate extensive phenotypic associations with APOE alleles in a large, diverse cohort, despite limitations in accuracy for EHR-derived phenotypes. We provide a comprehensive catalog of APOE -associated phenotypes and present evidence of unique phenotypic associations by sex and ancestry, as well as heterogeneity in effect size across ancestry.- Published
- 2024
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38. Higher odds of squamous cell carcinoma in sexual minority males compared to heterosexual males is mediated by HIV status in a mediation analysis of 13,687 participants.
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Curtis KL, Stubblefield O, Goleva SB, Denny JC, and Lipner SR
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- 2024
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39. Replicating the Association of Variants in BSN and APBA1 with Obesity in Diverse Populations.
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Robinson JR, Denny JC, and Zeng C
- Abstract
In a recent study by Zhao et al., rare protein-truncating variants (PTVs) in the BSN and APBA1 genes showed effects on obesity that exceeded those of well-known genes such as MC4R in a UK cohort. In this study, we leveraged the All of Us Research Program, to investigate the association of predicted LoF (pLoF) PTVs in BSN and APBA1 with body mass index (BMI) across a population of diverse ancestry. Our analysis revealed that the impact of pLoF variants in BSN and APBA1 on BMI was notably greater in this cohort, especially among individuals of European ancestry. Additionally, a phenome-wide association study (PheWAS) using the extensive phenotypic data available in the All of Us Research Program uncovered novel associations of BSN and APBA1 heterozygous pLoF carriers with various phenotypes. Specifically, BSN pLoF variants were associated with pulmonary hypertension, atrial fibrillation, and anticoagulant use, while APBA1 pLoF variants were linked to disorders of the temporomandibular joint. These findings underscore the potential of large-scale biobanks in advancing genetic discovery.
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- 2024
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40. Frequency of pharmacogenomic variation and medication exposures among All of Us Participants.
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Haddad A, Radhakrishnan A, McGee S, Smith JD, Karnes JH, Venner E, Wheeler MM, Patterson K, Walker K, Kalra D, Kalla SE, Wang Q, Gibbs RA, Jarvik GP, Sanchez J, Musick A, Ramirez AH, Denny JC, and Empey PE
- Abstract
Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in studies impedes clinical translation and equitable application of precision medicine. We evaluated the frequencies of PGx variants, predicted phenotypes, and medication exposures using whole genome sequencing and EHR data from nearly 100k diverse All of Us Research Program participants. We report 100% of participants carried at least one pharmacogenomics variant and nearly all (99.13%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with over 20% having both an actionable phenotype and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we also report hundreds of alleles and predicted phenotypes that deviate from known frequencies and/or were previously unreported, including within admixed American and African ancestry groups.
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- 2024
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41. Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
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Keaton JM, Kamali Z, Xie T, Vaez A, Williams A, Goleva SB, Ani A, Evangelou E, Hellwege JN, Yengo L, Young WJ, Traylor M, Giri A, Zheng Z, Zeng J, Chasman DI, Morris AP, Caulfield MJ, Hwang SJ, Kooner JS, Conen D, Attia JR, Morrison AC, Loos RJF, Kristiansson K, Schmidt R, Hicks AA, Pramstaller PP, Nelson CP, Samani NJ, Risch L, Gyllensten U, Melander O, Riese H, Wilson JF, Campbell H, Rich SS, Psaty BM, Lu Y, Rotter JI, Guo X, Rice KM, Vollenweider P, Sundström J, Langenberg C, Tobin MD, Giedraitis V, Luan J, Tuomilehto J, Kutalik Z, Ripatti S, Salomaa V, Girotto G, Trompet S, Jukema JW, van der Harst P, Ridker PM, Giulianini F, Vitart V, Goel A, Watkins H, Harris SE, Deary IJ, van der Most PJ, Oldehinkel AJ, Keavney BD, Hayward C, Campbell A, Boehnke M, Scott LJ, Boutin T, Mamasoula C, Järvelin MR, Peters A, Gieger C, Lakatta EG, Cucca F, Hui J, Knekt P, Enroth S, De Borst MH, Polašek O, Concas MP, Catamo E, Cocca M, Li-Gao R, Hofer E, Schmidt H, Spedicati B, Waldenberger M, Strachan DP, Laan M, Teumer A, Dörr M, Gudnason V, Cook JP, Ruggiero D, Kolcic I, Boerwinkle E, Traglia M, Lehtimäki T, Raitakari OT, Johnson AD, Newton-Cheh C, Brown MJ, Dominiczak AF, Sever PJ, Poulter N, Chambers JC, Elosua R, Siscovick D, Esko T, Metspalu A, Strawbridge RJ, Laakso M, Hamsten A, Hottenga JJ, de Geus E, Morris AD, Palmer CNA, Nolte IM, Milaneschi Y, Marten J, Wright A, Zeggini E, Howson JMM, O'Donnell CJ, Spector T, Nalls MA, Simonsick EM, Liu Y, van Duijn CM, Butterworth AS, Danesh JN, Menni C, Wareham NJ, Khaw KT, Sun YV, Wilson PWF, Cho K, Visscher PM, Denny JC, Levy D, Edwards TL, Munroe PB, Snieder H, and Warren HR
- Subjects
- Female, Humans, Male, Genetic Risk Score, Risk Factors, Blood Pressure genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Hypertension genetics, Multifactorial Inheritance, Polymorphism, Single Nucleotide
- Abstract
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10
-8 ) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126 ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44 ) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34 ). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research., (© 2024. The Author(s).)- Published
- 2024
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42. Overcome the Limitation of Phenome-Wide Association Studies (PheWAS): Extension of PheWAS to Efficient and Robust Large-Scale ICD Codes Analysis.
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Lin YC, Zhang S, Vessels T, Bastarache L, Bejan CA, Hsie RS, Philips EJ, Ruderfer DM, Pulley JM, Edwards TL, Wells QS, Warner JL, Denny JC, Roden DM, Kang H, and Xu Y
- Abstract
The Phenome-wide association studies (PheWAS) have become widely used for efficient, high-throughput evaluation of relationship between a genetic factor and a large number of disease phenotypes, typically extracted from a DNA biobank linked with electronic medical records (EMR). Phecodes, billing code-derived disease case-control status, are usually used as outcome variables in PheWAS and logistic regression has been the standard choice of analysis method. Since the clinical diagnoses in EMR are often inaccurate with errors which can lead to biases in the odds ratio estimates, much effort has been put to accurately define the cases and controls to ensure an accurate analysis. Specifically in order to correctly classify controls in the population, an exclusion criteria list for each Phecode was manually compiled to obtain unbiased odds ratios. However, the accuracy of the list cannot be guaranteed without extensive data curation process. The costly curation process limits the efficiency of large-scale analyses that take full advantage of all structured phenotypic information available in EMR. Here, we proposed to estimate relative risks (RR) instead. We first demonstrated the desired nature of R R that overcomes the inaccuracy in the controls via theoretical formula. With simulation and real data application, we further confirmed that R R is unbiased without compiling exclusion criteria lists. With R R as estimates, we are able to efficiently extend PheWAS to a larger-scale, phenome construction agnostic analysis of phenotypes, using ICD 9/10 codes, which preserve much more disease-related clinical information than Phecodes., Competing Interests: Competing Interest Statement The authors have declared no competing interest.
- Published
- 2024
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43. Comparison of phenomic profiles in the All of Us Research Program against the US general population and the UK Biobank.
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Zeng C, Schlueter DJ, Tran TC, Babbar A, Cassini T, Bastarache LA, and Denny JC
- Subjects
- Humans, Biological Specimen Banks, UK Biobank, Phenotype, United Kingdom epidemiology, Phenomics, Population Health
- Abstract
Importance: Knowledge gained from cohort studies has dramatically advanced both public and precision health. The All of Us Research Program seeks to enroll 1 million diverse participants who share multiple sources of data, providing unique opportunities for research. It is important to understand the phenomic profiles of its participants to conduct research in this cohort., Objectives: More than 280 000 participants have shared their electronic health records (EHRs) in the All of Us Research Program. We aim to understand the phenomic profiles of this cohort through comparisons with those in the US general population and a well-established nation-wide cohort, UK Biobank, and to test whether association results of selected commonly studied diseases in the All of Us cohort were comparable to those in UK Biobank., Materials and Methods: We included participants with EHRs in All of Us and participants with health records from UK Biobank. The estimates of prevalence of diseases in the US general population were obtained from the Global Burden of Diseases (GBD) study. We conducted phenome-wide association studies (PheWAS) of 9 commonly studied diseases in both cohorts., Results: This study included 287 012 participants from the All of Us EHR cohort and 502 477 participants from the UK Biobank. A total of 314 diseases curated by the GBD were evaluated in All of Us, 80.9% (N = 254) of which were more common in All of Us than in the US general population [prevalence ratio (PR) >1.1, P < 2 × 10-5]. Among 2515 diseases and phenotypes evaluated in both All of Us and UK Biobank, 85.6% (N = 2152) were more common in All of Us (PR >1.1, P < 2 × 10-5). The Pearson correlation coefficients of effect sizes from PheWAS between All of Us and UK Biobank were 0.61, 0.50, 0.60, 0.57, 0.40, 0.53, 0.46, 0.47, and 0.24 for ischemic heart diseases, lung cancer, chronic obstructive pulmonary disease, dementia, colorectal cancer, lower back pain, multiple sclerosis, lupus, and cystic fibrosis, respectively., Discussion: Despite the differences in prevalence of diseases in All of Us compared to the US general population or the UK Biobank, our study supports that All of Us can facilitate rapid investigation of a broad range of diseases., Conclusion: Most diseases were more common in All of Us than in the general US population or the UK Biobank. Results of disease-disease association tests from All of Us are comparable to those estimated in another well-studied national cohort., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)
- Published
- 2024
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44. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.
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Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X, Lorenz KM, Mandla R, Huerta-Chagoya A, Melloni GEM, Kanoni S, Rayner NW, Bocher O, Arruda AL, Sonehara K, Namba S, Lee SSK, Preuss MH, Petty LE, Schroeder P, Vanderwerff B, Kals M, Bragg F, Lin K, Guo X, Zhang W, Yao J, Kim YJ, Graff M, Takeuchi F, Nano J, Lamri A, Nakatochi M, Moon S, Scott RA, Cook JP, Lee JJ, Pan I, Taliun D, Parra EJ, Chai JF, Bielak LF, Tabara Y, Hai Y, Thorleifsson G, Grarup N, Sofer T, Wuttke M, Sarnowski C, Gieger C, Nousome D, Trompet S, Kwak SH, Long J, Sun M, Tong L, Chen WM, Nongmaithem SS, Noordam R, Lim VJY, Tam CHT, Joo YY, Chen CH, Raffield LM, Prins BP, Nicolas A, Yanek LR, Chen G, Brody JA, Kabagambe E, An P, Xiang AH, Choi HS, Cade BE, Tan J, Broadaway KA, Williamson A, Kamali Z, Cui J, Thangam M, Adair LS, Adeyemo A, Aguilar-Salinas CA, Ahluwalia TS, Anand SS, Bertoni A, Bork-Jensen J, Brandslund I, Buchanan TA, Burant CF, Butterworth AS, Canouil M, Chan JCN, Chang LC, Chee ML, Chen J, Chen SH, Chen YT, Chen Z, Chuang LM, Cushman M, Danesh J, Das SK, de Silva HJ, Dedoussis G, Dimitrov L, Doumatey AP, Du S, Duan Q, Eckardt KU, Emery LS, Evans DS, Evans MK, Fischer K, Floyd JS, Ford I, Franco OH, Frayling TM, Freedman BI, Genter P, Gerstein HC, Giedraitis V, González-Villalpando C, González-Villalpando ME, Gordon-Larsen P, Gross M, Guare LA, Hackinger S, Hakaste L, Han S, Hattersley AT, Herder C, Horikoshi M, Howard AG, Hsueh W, Huang M, Huang W, Hung YJ, Hwang MY, Hwu CM, Ichihara S, Ikram MA, Ingelsson M, Islam MT, Isono M, Jang HM, Jasmine F, Jiang G, Jonas JB, Jørgensen T, Kamanu FK, Kandeel FR, Kasturiratne A, Katsuya T, Kaur V, Kawaguchi T, Keaton JM, Kho AN, Khor CC, Kibriya MG, Kim DH, Kronenberg F, Kuusisto J, Läll K, Lange LA, Lee KM, Lee MS, Lee NR, Leong A, Li L, Li Y, Li-Gao R, Ligthart S, Lindgren CM, Linneberg A, Liu CT, Liu J, Locke AE, Louie T, Luan J, Luk AO, Luo X, Lv J, Lynch JA, Lyssenko V, Maeda S, Mamakou V, Mansuri SR, Matsuda K, Meitinger T, Melander O, Metspalu A, Mo H, Morris AD, Moura FA, Nadler JL, Nalls MA, Nayak U, Ntalla I, Okada Y, Orozco L, Patel SR, Patil S, Pei P, Pereira MA, Peters A, Pirie FJ, Polikowsky HG, Porneala B, Prasad G, Rasmussen-Torvik LJ, Reiner AP, Roden M, Rohde R, Roll K, Sabanayagam C, Sandow K, Sankareswaran A, Sattar N, Schönherr S, Shahriar M, Shen B, Shi J, Shin DM, Shojima N, Smith JA, So WY, Stančáková A, Steinthorsdottir V, Stilp AM, Strauch K, Taylor KD, Thorand B, Thorsteinsdottir U, Tomlinson B, Tran TC, Tsai FJ, Tuomilehto J, Tusie-Luna T, Udler MS, Valladares-Salgado A, van Dam RM, van Klinken JB, Varma R, Wacher-Rodarte N, Wheeler E, Wickremasinghe AR, van Dijk KW, Witte DR, Yajnik CS, Yamamoto K, Yamamoto K, Yoon K, Yu C, Yuan JM, Yusuf S, Zawistowski M, Zhang L, Zheng W, Raffel LJ, Igase M, Ipp E, Redline S, Cho YS, Lind L, Province MA, Fornage M, Hanis CL, Ingelsson E, Zonderman AB, Psaty BM, Wang YX, Rotimi CN, Becker DM, Matsuda F, Liu Y, Yokota M, Kardia SLR, Peyser PA, Pankow JS, Engert JC, Bonnefond A, Froguel P, Wilson JG, Sheu WHH, Wu JY, Hayes MG, Ma RCW, Wong TY, Mook-Kanamori DO, Tuomi T, Chandak GR, Collins FS, Bharadwaj D, Paré G, Sale MM, Ahsan H, Motala AA, Shu XO, Park KS, Jukema JW, Cruz M, Chen YI, Rich SS, McKean-Cowdin R, Grallert H, Cheng CY, Ghanbari M, Tai ES, Dupuis J, Kato N, Laakso M, Köttgen A, Koh WP, Bowden DW, Palmer CNA, Kooner JS, Kooperberg C, Liu S, North KE, Saleheen D, Hansen T, Pedersen O, Wareham NJ, Lee J, Kim BJ, Millwood IY, Walters RG, Stefansson K, Ahlqvist E, Goodarzi MO, Mohlke KL, Langenberg C, Haiman CA, Loos RJF, Florez JC, Rader DJ, Ritchie MD, Zöllner S, Mägi R, Marston NA, Ruff CT, van Heel DA, Finer S, Denny JC, Yamauchi T, Kadowaki T, Chambers JC, Ng MCY, Sim X, Below JE, Tsao PS, Chang KM, McCarthy MI, Meigs JB, Mahajan A, Spracklen CN, Mercader JM, Boehnke M, Rotter JI, Vujkovic M, Voight BF, Morris AP, and Zeggini E
- Subjects
- Humans, Adipocytes metabolism, Chromatin genetics, Chromatin metabolism, Coronary Artery Disease complications, Coronary Artery Disease genetics, Diabetic Nephropathies complications, Diabetic Nephropathies genetics, Endothelial Cells metabolism, Enteroendocrine Cells, Epigenomics, Islets of Langerhans metabolism, Multifactorial Inheritance genetics, Peripheral Arterial Disease complications, Peripheral Arterial Disease genetics, Single-Cell Analysis, Diabetes Mellitus, Type 2 classification, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 pathology, Diabetes Mellitus, Type 2 physiopathology, Disease Progression, Genetic Predisposition to Disease genetics, Genome-Wide Association Study
- Abstract
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes
1,2 and molecular mechanisms that are often specific to cell type3,4 . Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8 ) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care., (© 2024. The Author(s).)- Published
- 2024
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45. The All of Us Research Program is an opportunity to enhance the diversity of US biomedical research.
- Author
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Bianchi DW, Brennan PF, Chiang MF, Criswell LA, D'Souza RN, Gibbons GH, Gilman JK, Gordon JA, Green ED, Gregurick S, Hodes RJ, Kilmarx PH, Koob GF, Koroshetz WJ, Langevin HM, Lorsch JR, Marrazzo JM, Pérez-Stable EJ, Rathmell WK, Rodgers GP, Rutter JL, Simoni JM, Tromberg BJ, Tucci DL, Volkow ND, Woychik R, Zenk SN, Kozlowski E, Peterson RS, Ginsburg GS, and Denny JC
- Subjects
- Humans, Mentors, Population Health, Biomedical Research
- Published
- 2024
- Full Text
- View/download PDF
46. Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program.
- Author
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Schlueter DJ, Sulieman L, Mo H, Keaton JM, Ferrara TM, Williams A, Qian J, Stubblefield O, Zeng C, Tran TC, Bastarache L, Dai J, Babbar A, Ramirez A, Goleva SB, and Denny JC
- Subjects
- Humans, Phenotype, Polymorphism, Single Nucleotide, Smoking, Genome-Wide Association Study methods, Population Health
- Abstract
Objective: The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations., Materials and Methods: We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals., Results: PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10-5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated., Discussion: Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results., Conclusion: This study demonstrated the feasibility of studying common exposures using All of Us data., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2023.)
- Published
- 2023
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47. Data-driven science and diversity in the All of Us Research Program.
- Author
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Ginsburg GS, Denny JC, and Schully SD
- Subjects
- Humans, United States, Data Science, National Institutes of Health (U.S.), Population Health, Biomedical Research
- Abstract
The National Institutes of Health's All of Us Research Program is an accessible platform that hosts genomic and phenotypic data to be collected from 1 million participants in the United States. Its mission is to accelerate medical research and clinical breakthroughs with a special emphasis on diversity.
- Published
- 2023
- Full Text
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48. A test of automated use of electronic health records to aid in diagnosis of genetic disease.
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Cassini T, Bastarache L, Zeng C, Han ST, Wang J, He J, and Denny JC
- Subjects
- Humans, Electronic Health Records, Delayed Diagnosis, DNA, Mutation, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis diagnosis, Cystic Fibrosis genetics, Cystic Fibrosis pathology
- Abstract
Purpose: Automated use of electronic health records may aid in decreasing the diagnostic delay for rare diseases. The phenotype risk score (PheRS) is a weighted aggregate of syndromically related phenotypes that measures the similarity between an individual's conditions and features of a disease. For some diseases, there are individuals without a diagnosis of that disease who have scores similar to diagnosed patients. These individuals may have that disease but not yet be diagnosed., Methods: We calculated the PheRS for cystic fibrosis (CF) for 965,626 subjects in the Vanderbilt University Medical Center electronic health record., Results: Of the 400 subjects with the highest PheRS for CF, 248 (62%) had been diagnosed with CF. Twenty-six of the remaining participants, those who were alive and had DNA available in the linked DNA biobank, underwent clinical review and sequencing analysis of CFTR and SERPINA1. This uncovered a potential diagnosis for 2 subjects, 1 with CF and 1 with alpha-1-antitrypsin deficiency. An additional 7 subjects had pathogenic or likely pathogenic variants, 2 in CFTR and 5 in SERPINA1., Conclusion: These findings may be clinically actionable for the providers caring for these patients. Importantly, this study highlights feasibility and challenges for future implications of this approach., Competing Interests: Conflict of Interest L.B. is a consultant for Galatea Bio. L.B. and J.C.D. receive royalties from Nashville Biosciences for their application of phenome-wide association studies within BioVU. All other authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
49. Author Correction: Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection.
- Author
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Ferar K, Hall TO, Crawford DC, Rowley R, Satterfield BA, Li R, Gragert L, Karlson EW, de Andrade M, Kullo IJ, McCarty CA, Kho A, Hayes MG, Ritchie MD, Crane PK, Mirel DB, Carlson C, Connolly JJ, Hakonarson H, Crenshaw AT, Carrell D, Luo Y, Dikilitas O, Denny JC, Jarvik GP, and Crosslin DR
- Published
- 2023
- Full Text
- View/download PDF
50. Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection.
- Author
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Ferar K, Hall TO, Crawford DC, Rowley R, Satterfield BA, Li R, Gragert L, Karlson EW, de Andrade M, Kullo IJ, McCarty CA, Kho A, Hayes MG, Ritchie MD, Crane PK, Mirel DB, Carlson C, Connolly JJ, Hakonarson H, Crenshaw AT, Carrell D, Luo Y, Dikilitas O, Denny JC, Jarvik GP, and Crosslin DR
- Subjects
- Humans, Diarrhea, Histocompatibility Antigens, HLA Antigens genetics, Histocompatibility Antigens Class II, Genetic Variation, Genome-Wide Association Study, Clostridium Infections genetics
- Abstract
Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10
-14 ; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
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