128 results on '"Monda, Kl"'
Search Results
2. How well can familial hypercholesterolemia be identified in an electronic health record database?
- Author
-
Mues KE, Bogdanov AN, Monda KL, Yedigarova L, Liede A, and Kallenbach L
- Subjects
Familial hypercholesterolemia ,Dutch lipid network criteria ,electronic health record ,SNOMED ,Infectious and parasitic diseases ,RC109-216 - Abstract
Katherine E Mues,1 Alina N Bogdanov,2 Keri L Monda,1 Larisa Yedigarova,3 Alexander Liede,1 Lee Kallenbach2 1Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 2Practice Fusion, San Francisco, CA, USA; 3US Medical Affairs, Amgen Inc., Thousand Oaks, CA, USA Background: Familial hypercholesterolemia (FH) is a condition characterized by high cholesterol levels and increased risk for coronary heart disease (CHD) that often goes undiagnosed. The Dutch Lipid Network Criteria (DLNC) are used to identify FH in clinical settings via physical examination, personal and family history of CHD, in addition to the presence of deleterious mutations of the LDLR, ApoB, and PCSK9 genes. Agreement between clinical and genetic diagnosis of FH varies. While an ICD diagnosis code was not available for coding FH until 2016, Systematized Nomenclature of Medicine (SNOMED) clinical concept codes, including genetic diagnoses, for FH have been utilized in electronic health records (EHRs). Objective: To evaluate the concordance of identifying FH via SNOMED and ICD-10 CM codes vs the DLNC in an EHR database. Methods: Using the Practice Fusion EHR database, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated comparing an FH cohort identified via SNOMED and ICD-10 CM codes to one identified via the DLNC. Results: Among 907,616 patients with hypercholesterolemia, 2,180 were identified as FH via SNOMED code (zero were identified via ICD-10 CM), 259 had a DLNC score 6–8 (probable FH), and 45 had a DLNC score >8 (definite FH). Compared to DLNC score >8, the sensitivity, specificity, and PPV of the FH SNOMED code were 84.4%, 99.4%, and 6.4%, respectively. Compared to DLNC score ≥6, the sensitivity was 36.8% and the specificity was 99.5% with a PPV of 18.7%. Conclusion: Compared to the clinical criteria for FH, identification of FH patients via SNOMED diagnosis codes had high sensitivity and specificity, but low PPV. The discordance of these two techniques in identifying FH patients speaks to the challenges in identifying FH patients in large electronic databases such as administrative claims and EHR. Keywords: familial hypercholesterolemia, Dutch Lipid Network Criteria, electronic health record, SNOMED
- Published
- 2018
3. Quality control and conduct of genome-wide association meta-analyses
- Author
-
Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra BA, Ouwehand WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, Zillikens MC, Zitting P, Zondervan KT, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis, G, Absher, D, Alavere, H, Albrecht, E, Allen, H, Almgren, P, Amin, N, Amouyel, P, Anderson, D, Arnold, A, Arveiler, D, Aspelund, T, Asselbergs, F, Assimes, T, Atalay, M, Attwood, A, Atwood, L, Bakker, S, Balkau, B, Balmforth, A, Barlassina, C, Barroso, I, Basart, H, Bauer, S, Beckmann, J, Beilby, J, Bennett, A, Ben Shlomo, Y, Bergman, R, Bergmann, S, Berndt, S, Biffar, R, Di Blasio, A, Boehm, B, Boehnke, M, Boeing, H, Boerwinkle, E, Bolton, J, Bonnefond, A, Bonnycastle, L, Boomsma, D, Borecki, I, Bornstein, S, Bouatia Naji, N, Boucher, G, Bragg Gresham, J, Brambilla, P, Bruinenberg, M, Buchanan, T, Buechler, C, Cadby, G, Campbell, H, Caulfield, M, Cavalcanti Proença, C, Cesana, G, Chanock, S, Chasman, D, Chen, Y, Chines, P, Clegg, D, Coin, L, Collins, F, Connell, J, Cookson, W, Cooper, M, Cupples, L, Cusi, D, Day, I, Dedoussis, G, Dei, M, Deloukas, P, Dermitzakis, E, Dimas, A, Dimitriou, M, Dixon, A, Dörr, M, van Duijn, C, Ebrahim, S, Edkins, S, Eiriksdottir, G, Eisinger, K, Eklund, N, Elliott, P, Erbel, R, Erdmann, J, Erdos, M, Eriksson, J, Estrada, K, Evans, D, de Faire, U, Farrall, M, Feitosa, M, Ferrario, M, Ferrières, J, Fischer, K, Fisher, E, Fowkes, G, Fox, C, Franke, L, Franks, P, Fraser, R, Frau, F, Frayling, T, Freimer, N, Froguel, P, Fu, M, Gaget, S, Ganna, A, Gejman, P, Gentilini, D, Geus, E, Gieger, C, Gigante, B, Gjesing, A, Glazer, N, Goddard, M, Goel, A, Grallert, H, Gräßler, J, Grönberg, H, Groop, L, Groves, C, Gudnason, V, Guiducci, C, Gyllensten, U, Hall, A, Hall, P, Hallmans, G, Hamsten, A, Hansen, T, Haritunians, T, Harris, T, van der Harst, P, Hartikainen, A, Hassanali, N, Hattersley, A, Havulinna, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, den Heijer, M, Hengstenberg, C, Herzig, K, Hicks, A, Hingorani, A, Hinney, A, Hirschhorn, J, Hofman, A, Holmes, C, Homuth, G, Hottenga, J, Hovingh, K, Hu, F, Hu, Y, Huffman, J, Hui, J, Huikuri, H, Humphries, S, Hung, J, Hunt, S, Hunter, D, Hveem, K, Hyppönen, E, Igl, W, Illig, T, Ingelsson, E, Iribarren, C, Isomaa, B, Jackson, A, Jacobs, K, James, A, Jansson, J, Jarick, I, Jarvelin, M, Jöckel, K, Johansson, Å, Johnson, T, Jolley, J, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kähönen, M, Kajantie, E, Kanoni, S, Kao, W, Kaplan, L, Kaplan, R, Kaprio, J, Kapur, K, Karpe, F, Kathiresan, S, Kee, F, Keinanen Kiukaanniemi, S, Ketkar, S, Kettunen, J, Khaw, K, Kiemeney, L, Kinnunen, L, Kivimaki, M, Kivmaki, M, Van der Klauw, M, Kleber, M, Knowles, J, Koenig, W, Kolcic, I, Kolovou, G, König, I, Koskinen, S, Kovacs, P, Kraft, P, Kraja, A, Kristiansson, K, Krjutåjkov, K, Kroemer, H, Krohn, J, Krzelj, V, Kuh, D, Kulzer, J, Kumari, M, Kuulasmaa, K, Kuusisto, J, Kvaloy, K, Laakso, M, Laitinen, J, Lakka, T, Lamina, C, Langenberg, C, Lantieri, O, Lathrop, G, Launer, L, Lawlor, D, Lawrence, R, Leach, I, Lecoeur, C, Lee, S, Lehtimäki, T, Leitzmann, M, Lettre, G, Levinson, D, Li, G, Li, S, Liang, L, Lin, D, Lind, L, Lindgren, C, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Loley, C, Lorentzon, M, Luben, R, Ludwig, B, Madden, P, Magnusson, P, Mangino, M, Manunta, P, Marek, D, Marre, M, Martin, N, März, W, Maschio, A, Mathieson, I, Mcardle, W, Mccaroll, S, Mccarthy, A, Mccarthy, M, Mcknight, B, Medina Gomez, C, Medland, S, Meitinger, T, Metspalu, A, van Meurs, J, Meyre, D, Midthjell, K, Mihailov, E, Milani, L, Min, J, Moebus, S, Moffatt, M, Mohlke, K, Molony, C, Monda, K, Montgomery, G, Mooser, V, Morken, M, Morris, A, Mühleisen, T, Müller Nurasyid, M, Munroe, P, Musk, A, Narisu, N, Navis, G, Neale, B, Nelis, M, Nemesh, J, Neville, M, Ngwa, J, Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Psychiatry, EMGO - Mental health, Plastic, Reconstructive and Hand Surgery, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Biological Psychology, EMGO+ - Mental Health, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Abecasis, GR., Absher, D., Alavere, H., Albrecht, E., Allen, HL., Almgren, P., Amin, N., Amouyel, P., Anderson, D., Arnold, AM., Arveiler, D., Aspelund, T., Asselbergs, FW., Assimes, TL., Atalay, M., Attwood, AP., Atwood, LD., Bakker, SJ., Balkau, B., Balmforth, AJ., Barlassina, C., Barroso£££Inês£££ I., Basart, H., Bauer, S., Beckmann, JS., Beilby, JP., Bennett, AJ., Ben-Shlomo, Y., Bergman, RN., Bergmann, S., Berndt, SI., Biffar, R., Di Blasio AM., Boehm, BO., Boehnke, M., Boeing, H., Boerwinkle, E., Bolton, JL., Bonnefond, A., Bonnycastle, LL., Boomsma, DI., Borecki, IB., Bornstein, SR., Bouatia-Naji, N., Boucher, G., Bragg-Gresham, JL., Brambilla, P., Bruinenberg, M., Buchanan, TA., Buechler, C., Cadby, G., Campbell, H., Caulfield, MJ., Cavalcanti-Proença, C., Cesana, G., Chanock, SJ., Chasman, DI., Chen, YD., Chines, PS., Clegg, DJ., Coin, L., Collins, FS., Connell, JM., Cookson, W., Cooper, MN., Croteau-Chonka, DC., Cupples, LA., Cusi, D., Day, FR., Day, IN., Dedoussis, GV., Dei, M., Deloukas, P., Dermitzakis, ET., Dimas, AS., Dimitriou, M., Dixon, AL., Dörr, M., van Duijn CM., Ebrahim, S., Edkins, S., Eiriksdottir, G., Eisinger, K., Eklund, N., Elliott, P., Erbel, R., Erdmann, J., Erdos, MR., Eriksson, JG., Esko£££Tõnu£££ T., Estrada, K., Evans, DM., de Faire, U., Fall, T., Farrall, M., Feitosa, MF., Ferrario, MM., Ferreira, T., Ferrières, J., Fischer, K., Fisher, E., Fowkes, G., Fox, CS., Franke, L., Franks, PW., Fraser, RM., Frau, F., Frayling, T., Freimer, NB., Froguel, P., Fu, M., Gaget, S., Ganna, A., Gejman, PV., Gentilini, D., Geus, EJ., Gieger, C., Gigante, B., Gjesing, AP., Glazer, NL., Goddard, ME., Goel, A., Grallert, H., Gräßler, J., Grönberg, H., Groop, LC., Groves, CJ., Gudnason, V., Guiducci, C., Gustafsson, S., Gyllensten, U., Hall, AS., Hall, P., Hallmans, G., Hamsten, A., Hansen, T., Haritunians, T., Harris, TB., van der Harst, P., Hartikainen, AL., Hassanali, N., Hattersley, AT., Havulinna, AS., Hayward, C., Heard-Costa, NL., Heath, AC., Hebebrand, J., Heid, IM., den Heijer, M., Hengstenberg, C., Herzig, KH., Hicks, AA., Hingorani, A., Hinney, A., Hirschhorn, JN., Hofman, A., Holmes, CC., Homuth, G., Hottenga, JJ., Hovingh, KG., Hu, FB., Hu, YJ., Huffman, JE., Hui, J., Huikuri, H., Humphries, SE., Hung, J., Hunt, SE., Hunter, D., Hveem, K., Hyppönen, E., Igl, W., Illig, T., Ingelsson, E., Iribarren, C., Isomaa, B., Jackson, AU., Jacobs, KB., James, AL., Jansson, JO., Jarick, I., Jarvelin, MR., Jöckel, KH., Johansson£££Åsa£££ Å., Johnson, T., Jolley, J., Jørgensen, T., Jousilahti, P., Jula, A., Justice, AE., Kaakinen, M., Kähönen, M., Kajantie, E., Kanoni, S., Kao, WH., Kaplan, LM., Kaplan, RC., Kaprio, J., Kapur, K., Karpe, F., Kathiresan, S., Kee, F., Keinanen-Kiukaanniemi, SM., Ketkar, S., Kettunen, J., Khaw, KT., Kiemeney, LA., Kilpeläinen, TO., Kinnunen, L., Kivimaki, M., Kivmaki, M., Van der Klauw MM., Kleber, ME., Knowles, JW., Koenig, W., Kolcic, I., Kolovou, G., König, IR., Koskinen, S., Kovacs, P., Kraft, P., Kraja, AT., Kristiansson, K., KrjutÅjkov, K., Kroemer, HK., Krohn, JP., Krzelj, V., Kuh, D., Kulzer, JR., Kumari, M., Kutalik£££Zoltán£££ Z., Kuulasmaa, K., Kuusisto, J., Kvaloy, K., Laakso, M., Laitinen, JH., Lakka, TA., Lamina, C., Langenberg, C., Lantieri, O., Lathrop, GM., Launer, LJ., Lawlor, DA., Lawrence, RW., Leach, IM., Lecoeur, C., Lee, SH., Lehtimäki, T., Leitzmann, MF., Lettre, G., Levinson, DF., Li, G., Li, S., Liang, L., Lin, DY., Lind, L., Lindgren, CM., Lindström, J., Liu, J., Liuzzi, A., Locke, AE., Lokki, ML., Loley, C., Loos, RJ., Lorentzon, M., Luan£££Jian'an£££ J., Luben, RN., Ludwig, B., Madden, PA., Mägi, R., Magnusson, PK., Mangino, M., Manunta, P., Marek, D., Marre, M., Martin, NG., März, W., Maschio, A., Mathieson, I., McArdle, WL., McCaroll, SA., McCarthy, A., McCarthy, MI., McKnight, B., Medina-Gomez, C., Medland, SE., Meitinger, T., Metspalu, A., van Meurs JB., Meyre, D., Midthjell, K., Mihailov, E., Milani, L., Min, JL., Moebus, S., Moffatt, MF., Mohlke, KL., Molony, C., Monda, KL., Montgomery, GW., Mooser, V., Morken, MA., Morris, AD., Morris, AP., Mühleisen, TW., Müller-Nurasyid, M., Munroe, PB., Musk, AW., Narisu, N., Navis, G., Neale, BM., Nelis, M., Nemesh, J., Neville, MJ., Ngwa, JS., Nicholson, G., Nieminen, MS., Njølstad, I., Nohr, EA., Nolte, IM., North, KE., Nöthen, MM., Nyholt, DR., O'Connell, JR., Ohlsson, C., Oldehinkel, AJ., van Ommen GJ., Ong, KK., Oostra, BA., Ouwehand, WH., Palmer, CN., Palmer, LJ., Palotie, A., Paré, G., Parker, AN., Paternoster, L., Pawitan, Y., Pechlivanis, S., Peden, JF., Pedersen, NL., Pedersen, O., Pellikka, N., Peltonen, L., Penninx, B., Perola, M., Perry, JR., Person, T., Peters, A., Peters, MJ., Pichler, I., Pietiläinen, KH., Platou, CG., Polasek, O., Pouta, A., Power, C., Pramstaller, PP., Preuss, M., Price, JF., Prokopenko, I., Province, MA., Psaty, BM., Purcell, S., Pütter, C., Qi, L., Quertermous, T., Radhakrishnan, A., Raitakari, O., Randall, JC., Rauramaa, R., Rayner, NW., Rehnberg, E., Rendon, A., Ridderstråle, M., Ridker, PM., Ripatti, S., Rissanen, A., Rivadeneira, F., Rivolta, C., Robertson, NR., Rose, LM., Rudan, I., Saaristo, TE., Sager, H., Salomaa, V., Samani, NJ., Sambrook, JG., Sanders, AR., Sandholt, C., Sanna, S., Saramies, J., Schadt, EE., Scherag, A., Schipf, S., Schlessinger, D., Schreiber, S., Schunkert, H., Schwarz, PE., Scott, LJ., Shi, J., Shin, SY., Shuldiner, AR., Shungin, D., Signorini, S., Silander, K., Sinisalo, J., Skrobek, B., Smit, JH., Smith, AV., Smith, GD., Snieder, H., Soranzo, N., Sørensen, TI., Sovio, U., Spector, TD., Speliotes, EK., Stančáková, A., Stark, K., Stefansson, K., Steinthorsdottir, V., Stephens, JC., Stirrups, K., Stolk, RP., Strachan, DP., Strawbridge, RJ., Stringham, HM., Stumvoll, M., Surakka, I., Swift, AJ., Syvanen, AC., Tammesoo, ML., Teder-Laving, M., Teslovich, TM., Teumer, A., Theodoraki, EV., Thomson, B., Thorand, B., Thorleifsson, G., Thorsteinsdottir, U., Timpson, NJ., Tönjes, A., Tregouet, DA., Tremoli, E., Trip, MD., Tuomi, T., Tuomilehto, J., Tyrer, J., Uda, M., Uitterlinden, AG., Usala, G., Uusitupa, M., Valle, TT., Vandenput, L., Vatin, V., Vedantam, S., de Vegt, F., Vermeulen, SH., Viikari, J., Virtamo, J., Visscher, PM., Vitart, V., Van Vliet-Ostaptchouk JV., Voight, BF., Vollenweider, P., Volpato, CB., Völzke, H., Waeber, G., Waite, LL., Wallaschofski, H., Walters, GB., Wang, Z., Wareham, NJ., Watanabe, RM., Watkins, H., Weedon, MN., Welch, R., Weyant, RJ., Wheeler, E., White, CC., Wichmann, HE., Widen, E., Wild, SH., Willemsen, G., Willer, CJ., Wilsgaard, T., Wilson, JF., van Wingerden, S., Winkelmann, BR., Winkler, TW., Witte, DR., Witteman, JC., Wolffenbuttel, BH., Wong, A., Wood, AR., Workalemahu, T., Wright, AF., Yang, J., Yarnell, JW., Zgaga, L., Zhao, JH., Zillikens, MC., Zitting, P., and Zondervan, KT.
- Subjects
Quality Control ,Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,media_common.quotation_subject ,quality control, GWAMAS ,Control (management) ,Medizin ,Genome-wide association study ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Software ,SDG 17 - Partnerships for the Goals ,Meta-Analysis as Topic ,Comparable size ,Quality (business) ,030304 developmental biology ,media_common ,Protocol (science) ,0303 health sciences ,business.industry ,Software package ,Data science ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Genome-Wide Association Study/methods ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,quality control ,genome-wide association meta-analyses ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
- Published
- 2014
4. Defining the role of common variation in the genomic and biological architecture of adult human height
- Author
-
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.
- Subjects
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.
- Published
- 2014
5. Development of algorithms for identifying fatal cardiovascular disease in Medicare claims
- Author
-
Xie, F, Colantonio, LD, Curtis, JR, Kilgore, ML, Levitan, EB, Monda, KL, Safford, MM, Taylor, B, Woodward, M, Muntner, P, Xie, F, Colantonio, LD, Curtis, JR, Kilgore, ML, Levitan, EB, Monda, KL, Safford, MM, Taylor, B, Woodward, M, and Muntner, P
- Abstract
Background: Cause of death is often not available in administrative claims data. Objective: To develop claims-based algorithms to identify deaths due to fatal cardiovascular disease (CVD; ie, fatal coronary heart disease [CHD] or stroke), CHD, and stroke. Methods: Reasons for Geographic and Racial Differences in Stroke (REGARDS) study data were linked with Medicare claims to develop the algorithms. Events adjudicated by REGARDS study investigators were used as the gold standard. Stepwise selection was used to choose predictors from Medicare data for inclusion in the algorithms. C-index, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess algorithm performance. Net reclassification index (NRI) was used to compare the algorithms with an approach of classifying all deaths within 28 days following hospitalization for myocardial infarction and stroke to be fatal CVD. Results: Data from 2,685 REGARDS participants with linkage to Medicare, who died between 2003 and 2013, were analyzed. The C-index for discriminating fatal CVD from other causes of death was 0.87. Using a cut-point that provided the closest observed-to-predicted number of fatal CVD events, the sensitivity was 0.64, specificity 0.90, PPV 0.65, and NPV 0.90. The algorithms resulted in positive NRIs compared with using deaths within 28 days following hospitalization for myocardial infarction and stroke. Claims-based algorithms for discriminating fatal CHD and fatal stroke performed similarly to fatal CVD. Conclusion: The claims-based algorithms developed to discriminate fatal CVD events from other causes of death performed better than the method of using hospital discharge diagnosis codes.
- Published
- 2018
6. Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States
- Author
-
Peters, SAE, Colantonio, LD, Zhao, H, Bittner, V, Dai, Y, Farkouh, ME, Monda, KL, Safford, MM, Muntner, P, Woodward, M, Peters, SAE, Colantonio, LD, Zhao, H, Bittner, V, Dai, Y, Farkouh, ME, Monda, KL, Safford, MM, Muntner, P, and Woodward, M
- Abstract
Background: Historically, women have been less likely than men to receive guideline-recommended statin therapy for the secondary prevention of myocardial infarction (MI). Objectives: The authors examined contemporary sex differences in prescription fills for high-intensity statin therapy following an MI, overall and across population subgroups, and assessed whether sex differences were attenuated following recent efforts to reduce sex disparities in the use of cardiovascular disease preventive therapies. Methods: The authors studied 16,898 (26% women) U.S. adults <65 years of age with commercial health insurance in the MarketScan database, and 71,358 (49% women) U.S. adults ≥66 years of age with government health insurance through Medicare who filled statin prescriptions within 30 days after hospital discharge for MI in 2014 to 2015. The authors calculated adjusted women-to-men risk ratios and 95% confidence intervals (CIs) for filling a high-intensity statin prescription (i.e., atorvastatin 40 to 80 mg, and rosuvastatin 20 to 40 mg) following hospital discharge for MI. Results: In 2014 to 2015, 56% of men and 47% of women filled a high-intensity statin following hospital discharge for MI. Adjusted risk ratios for filling a high-intensity statin comparing women with men were 0.91 (95% CI: 0.90 to 0.92) in the total population, 0.91 (95% CI: 0.89 to 0.92) among those with no prior statin use, and 0.87 (95% CI: 0.85 to 0.90) and 0.98 (95% CI: 0.97 to 1.00) for those taking low/moderate-intensity and high-intensity statins prior to their MI, respectively. Women were less likely than men to fill high-intensity statins within all subgroups analyzed, and the disparity was largest in the youngest and oldest adults and for those without prevalent comorbid conditions. Conclusions: Despite recent efforts to reduce sex differences in guideline-recommended therapy, women continue to be less likely than men to fill a prescription for high-intensity statins following hospitalizat
- Published
- 2018
7. Biological interpretation of genome-wide association studies using predicted gene functions
- Author
-
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
- Subjects
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
- Published
- 2015
8. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- Author
-
Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, LT, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, QB, Ngwa, JS, Renstrom, F, Quaye, L, Eicher, JD, Hayes, J E, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, WH, Zhao, W, Griffin, PJ, Haller, T, Ahmad, Shahzad, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikainen, LP, Huppertz, C, Willemsen, G, Peyrot, WJ, Wu, Fenny, Kristiansson, K, Demirkan, Ayse, Fornage, M, Hassinen, M, Bielak, LF, Cadby, G, Tanaka, T, Magl, R, van der Most, PJ, Jackson, AU, Bragg-Gresham, JL, Vitart, V, Marten, J, Navarro, P, Bellis, C, Pasko, D, Johansson, A, Snitker, S, Cheng, YC, Eriksson, J, Lim, U, Aadahl, M, Adair, LS, Amin, Najaf, Balkau, B, Auvinen, J, Beilby, J, Bergman, RN, Bergmann, S, Bertoni, AG, Blangero, J, Bonnefond, A, Bonnycastle, LL, Borja, JB, Brage, S, Busonero, F, Buyske, S, Campbell, H, Chines, PS, Collins, FS, Corre, T, Smith, GD, Delgado, GE, Dueker, N, Dorr, M, Ebeling, T, Eiriksdottir, G, Esko, T, Faul, JD, Fu, M, Faerch, K, Gieger, C, Glaser, S, Gong, J, Gordon-Larsen, P, Grallert, H, Grammer, TB, Grarup, N, Van Grootheest, G, Harald, K, Hastie, ND, Havulinna, AS, Hernandez, D, Hindorff, L, Hocking, LJ, Holmens, OL, Holzapfel, C, Hottenga, JJ, Huang, J, Huang, T, Hui, J, Huth, C, Hutri-Kahonen, N, James, AL, Jansson, JO, Jhun, MA, Juonala, M, Kinnunen, L, Koistinen, HA, Kolcic, I, Komulainen, P, Kuusisto, J, Kvaloy, K, Kahonen, M, Lakka, TA, Launer, LJ, Lehne, B, Lindgren, CM, Lorentzon, M, Luben, R, Marre, M (Michel), Milaneschi, Y, Monda, KL, Montgomery, GW, de Moor, MHM, Mulas, A, Muller-Nurasyid, M, Musk, AW, Mannikko, R, Mannisto, S, Narisu, N, Nauck, M, Nettleton, JA, Nolte, IM, Oldehinkel, AJ (A.), Olden, M, Ong, KK, Padmanabhan, S, Paternoster, L, Perez, J, Perola, M, Peters, A, Peters, U, Peyser, PA, Prokopenko, I, Puolijoki, H, Raitakari, OT, Rankinen, T, Rasmussen-Torvik, LJ, Rawal, R, Ridker, PM, Rose, LM, Rudan, I, Sarti, C, Sarzynski, MA, Savonen, K, Scott, WR, Sanna, S, Shuldiner, AR, Sidney, S, Silbernagel, G, Smith, BH, Smith, JA, Snieder, H, Stancakova, A, Sternfeld, B, Swift, AJ, Tammelin, T, Tan, ST, Thorand, B, Thuillier, D, Vandenput, L, Vestergaard, H, van Vliet-Ostaptchouk, JV, Vohl, MC, Volker, U, Waeber, G, Walker, M, Wild, S, Wong, A, Wright, AF, Zillikens, M.C., Zubair, N, Haiman, CA, LeMarchand, L, Gyllensten, U, Ohlsson, C, Ohlsson, CC, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Perusse, L, Wilson, JF, Hayward, C, Polasek, O, Cucca, F, Hveem, K, Hartman, CA, Tonjes, A, Bandinelli, S, Palmer, LJ, Kardia, SLR, Rauramaa, R, Sorensen, TIA, Tuomilehto, J, Salomaa, V, Penninx, B, de Geus, EJC, Boomsma, DI, Lehtimaki, T, Mangino, M, Laakso, M, Bouchard, C, Martin, NG, Kuh, D, Liu, YM, Linneberg, A, Marz, W, Strauch, K, Kivimaki, M, Harris, TB, Gudnason, V, Volzke, H, Qi, L, Jarvelin, MR, Chambers, JC, Kooner, JS, Froguel, P, Kooperberg, C, Vollenweider, P, Hallmans, G, Hansen, T, Pedersen, O, Metspalu, A, Wareham, NJ, Langenberg, C, Weir, DR, Porteous, DJ, Boerwinkle, E, Chasman, DI, Abecasis, GR, Barroso, I, McCarthy, MI, Frayling, TM, O'Connell, JR, Duijn, Cornelia, Boehnke, M, Heid, IM, Mohlke, KL, Strachan, DP, Fox, CS, Liu, CT, Hirschhorn, JN, Klein, RJ, Johnson, AD, Borecki, IB, Franks, PW, North, KE, Cupples, LA, Loos, RJF, Kilpelainen, TO, Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, LT, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, QB, Ngwa, JS, Renstrom, F, Quaye, L, Eicher, JD, Hayes, J E, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, WH, Zhao, W, Griffin, PJ, Haller, T, Ahmad, Shahzad, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikainen, LP, Huppertz, C, Willemsen, G, Peyrot, WJ, Wu, Fenny, Kristiansson, K, Demirkan, Ayse, Fornage, M, Hassinen, M, Bielak, LF, Cadby, G, Tanaka, T, Magl, R, van der Most, PJ, Jackson, AU, Bragg-Gresham, JL, Vitart, V, Marten, J, Navarro, P, Bellis, C, Pasko, D, Johansson, A, Snitker, S, Cheng, YC, Eriksson, J, Lim, U, Aadahl, M, Adair, LS, Amin, Najaf, Balkau, B, Auvinen, J, Beilby, J, Bergman, RN, Bergmann, S, Bertoni, AG, Blangero, J, Bonnefond, A, Bonnycastle, LL, Borja, JB, Brage, S, Busonero, F, Buyske, S, Campbell, H, Chines, PS, Collins, FS, Corre, T, Smith, GD, Delgado, GE, Dueker, N, Dorr, M, Ebeling, T, Eiriksdottir, G, Esko, T, Faul, JD, Fu, M, Faerch, K, Gieger, C, Glaser, S, Gong, J, Gordon-Larsen, P, Grallert, H, Grammer, TB, Grarup, N, Van Grootheest, G, Harald, K, Hastie, ND, Havulinna, AS, Hernandez, D, Hindorff, L, Hocking, LJ, Holmens, OL, Holzapfel, C, Hottenga, JJ, Huang, J, Huang, T, Hui, J, Huth, C, Hutri-Kahonen, N, James, AL, Jansson, JO, Jhun, MA, Juonala, M, Kinnunen, L, Koistinen, HA, Kolcic, I, Komulainen, P, Kuusisto, J, Kvaloy, K, Kahonen, M, Lakka, TA, Launer, LJ, Lehne, B, Lindgren, CM, Lorentzon, M, Luben, R, Marre, M (Michel), Milaneschi, Y, Monda, KL, Montgomery, GW, de Moor, MHM, Mulas, A, Muller-Nurasyid, M, Musk, AW, Mannikko, R, Mannisto, S, Narisu, N, Nauck, M, Nettleton, JA, Nolte, IM, Oldehinkel, AJ (A.), Olden, M, Ong, KK, Padmanabhan, S, Paternoster, L, Perez, J, Perola, M, Peters, A, Peters, U, Peyser, PA, Prokopenko, I, Puolijoki, H, Raitakari, OT, Rankinen, T, Rasmussen-Torvik, LJ, Rawal, R, Ridker, PM, Rose, LM, Rudan, I, Sarti, C, Sarzynski, MA, Savonen, K, Scott, WR, Sanna, S, Shuldiner, AR, Sidney, S, Silbernagel, G, Smith, BH, Smith, JA, Snieder, H, Stancakova, A, Sternfeld, B, Swift, AJ, Tammelin, T, Tan, ST, Thorand, B, Thuillier, D, Vandenput, L, Vestergaard, H, van Vliet-Ostaptchouk, JV, Vohl, MC, Volker, U, Waeber, G, Walker, M, Wild, S, Wong, A, Wright, AF, Zillikens, M.C., Zubair, N, Haiman, CA, LeMarchand, L, Gyllensten, U, Ohlsson, C, Ohlsson, CC, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Perusse, L, Wilson, JF, Hayward, C, Polasek, O, Cucca, F, Hveem, K, Hartman, CA, Tonjes, A, Bandinelli, S, Palmer, LJ, Kardia, SLR, Rauramaa, R, Sorensen, TIA, Tuomilehto, J, Salomaa, V, Penninx, B, de Geus, EJC, Boomsma, DI, Lehtimaki, T, Mangino, M, Laakso, M, Bouchard, C, Martin, NG, Kuh, D, Liu, YM, Linneberg, A, Marz, W, Strauch, K, Kivimaki, M, Harris, TB, Gudnason, V, Volzke, H, Qi, L, Jarvelin, MR, Chambers, JC, Kooner, JS, Froguel, P, Kooperberg, C, Vollenweider, P, Hallmans, G, Hansen, T, Pedersen, O, Metspalu, A, Wareham, NJ, Langenberg, C, Weir, DR, Porteous, DJ, Boerwinkle, E, Chasman, DI, Abecasis, GR, Barroso, I, McCarthy, MI, Frayling, TM, O'Connell, JR, Duijn, Cornelia, Boehnke, M, Heid, IM, Mohlke, KL, Strachan, DP, Fox, CS, Liu, CT, Hirschhorn, JN, Klein, RJ, Johnson, AD, Borecki, IB, Franks, PW, North, KE, Cupples, LA, Loos, RJF, and Kilpelainen, TO
- Published
- 2017
9. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- Author
-
Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, Loos, RJF, Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, Sara M., Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K, Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, Albertine J., Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, and Loos, RJF
- Published
- 2016
10. Biological interpretation of genome-wide association studies using predicted gene functions
- Author
-
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
11. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
- Author
-
Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, Loos, RJF, Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, and Loos, RJF
- Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap
- Published
- 2015
12. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
-
Berndt SI, Gustafsson S, Mxe4gi R, Ganna A, Wheeler E, Feitosa MF, Justice AE, Monda KL, Croteau-Chonka DC, Day FR, Esko T, Fall T, Ferreira T, Gentilini D, Jackson AU, Hottenga JJ, Willemsen G, Boomsma DI, Penninx B, Strachan DP, Thorsteinsdottir U, van Duijn CM, Visscher PM, Di Blasio AM, Hirschhorn JN, Lindgren CM, Morris AP, Meyre D, Scherag A, McCarthy MI, Speliotes EK, North KE, Loos RJ, and Ingelsson E
- Published
- 2013
13. Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
- Author
-
Randall, JC, Winkler, TW, Kutalik, Z, Berndt, SI, Jackson, AU, Monda, KL, Kilpeläinen, TO, Esko, T, Mägi, R, Li, S, Workalemahu, T, Feitosa, MF, Croteau-Chonka, DC, Day, FR, Fall, T, Ferreira, T, Gustafsson, S, Locke, AE, Mathieson, I, Scherag, A, Vedantam, S, Wood, AR, Liang, L, Steinthorsdottir, V, Thorleifsson, G, Dermitzakis, ET, Dimas, AS, Karpe, F, Min, JL, Nicholson, G, Clegg, DJ, Person, T, Krohn, JP, Bauer, S, Buechler, C, Eisinger, K, DIAGRAM Consortium, Bonnefond, A, Froguel, P, MAGIC Investigators, Hottenga, JJ, Prokopenko, I, Waite, LL, Harris, TB, Smith, AV, Shuldiner, AR, McArdle, WL, Caulfield, MJ, Munroe, PB, Grönberg, H, Chen, YD, Li, G, Beckmann, JS, Johnson, T, Thorsteinsdottir, U, Teder-Laving, M, Khaw, KT, Wareham, NJ, Zhao, JH, Amin, N, Oostra, BA, Kraja, AT, Province, MA, Cupples, LA, Heard-Costa, NL, Kaprio, J, Ripatti, S, Surakka, I, Collins, FS, Saramies, J, Tuomilehto, J, Jula, A, Salomaa, V, Erdmann, J, Hengstenberg, C, Loley, C, Schunkert, H, Lamina, C, Wichmann, HE, Albrecht, E, Gieger, C, Hicks, AA, Johansson, A, Pramstaller, PP, Kathiresan, S, Speliotes, EK, Penninx, B, Hartikainen, AL, Jarvelin, MR, Gyllensten, U, Boomsma, DI, Campbell, H, Wilson, JF, Chanock, SJ, Farrall, M, Goel, A, Medina-Gomez, C, Rivadeneira, F, Estrada, K, Uitterlinden, AG, Hofman, A, Zillikens, MC, den Heijer, M, Kiemeney, LA, Maschio, A, Hall, P, Tyrer, J, Teumer, A, Völzke, H, Kovacs, P, Tönjes, A, Mangino, M, Spector, TD, Hayward, C, Rudan, I, Hall, AS, Samani, NJ, Attwood, AP, Sambrook, JG, Hung, J, Palmer, LJ, Lokki, ML, Sinisalo, J, Boucher, G, Huikuri, H, Lorentzon, M, Ohlsson, C, Eklund, N, Eriksson, JG, Barlassina, C, Rivolta, C, Nolte, IM, Snieder, H, Van der Klauw, MM, Van Vliet-Ostaptchouk, JV, Gejman, PV, Shi, J, Jacobs, KB, Wang, Z, Bakker, SJ, Mateo Leach, I, Navis, G, van der Harst, P, Martin, NG, Medland, SE, Montgomery, GW, Yang, J, Chasman, DI, Ridker, PM, Rose, LM, Lehtimäki, T, Raitakari, O, Absher, D, Iribarren, C, Basart, H, Hovingh, KG, Hyppönen, E, Power, C, Anderson, D, Beilby, JP, Hui, J, Jolley, J, Sager, H, Bornstein, SR, Schwarz, PE, Kristiansson, K, Perola, M, Lindström, J, Swift, AJ, Uusitupa, M, Atalay, M, Lakka, TA, Rauramaa, R, Bolton, JL, Fowkes, G, Fraser, RM, Price, JF, Fischer, K, Krjutå Kov, K, Metspalu, A, Mihailov, E, Langenberg, C, Luan, J, Ong, KK, Chines, PS, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Edkins, S, Franks, PW, Hallmans, G, Shungin, D, Morris, AD, Palmer, CN, Erbel, R, Moebus, S, Nöthen, MM, Pechlivanis, S, Hveem, K, Narisu, N, Hamsten, A, Humphries, SE, Strawbridge, RJ, Tremoli, E, Grallert, H, Thorand, B, Illig, T, Koenig, W, Müller-Nurasyid, M, Peters, A, Boehm, BO, Kleber, ME, März, W, Winkelmann, BR, Kuusisto, J, Laakso, M, Arveiler, D, Cesana, G, Kuulasmaa, K, Virtamo, J, Yarnell, JW, Kuh, D, Wong, A, Lind, L, de Faire, U, Gigante, B, Magnusson, PK, Pedersen, NL, Dedoussis, G, Dimitriou, M, Kolovou, G, Kanoni, S, Stirrups, K, Bonnycastle, LL, Njølstad, I, Wilsgaard, T, Ganna, A, Rehnberg, E, Hingorani, A, Kivimaki, M, Kumari, M, Assimes, TL, Barroso, I, Boehnke, M, Borecki, IB, Deloukas, P, Fox, CS, Frayling, T, Groop, LC, Haritunians, T, Hunter, D, Ingelsson, E, Kaplan, R, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, van Duijn, CM, Abecasis, GR, McCarthy, MI, Hirschhorn, JN, Qi, L, Loos, RJ, Lindgren, CM, North, KE, Heid, IM, Hjelt Institute (-2014), Department of Public Health, Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, Haartman Institute (-2014), Transplantation Laboratory, Kardiologian yksikkö, Department of Medicine, Clinicum, Department of General Practice and Primary Health Care, Diabetes and Obesity Research Program, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM Consortium, MAGIC Investigators, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Epidemiology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Internal Medicine, Public Health, Surgery, Medical Research Council (MRC), and Dermitzakis, Emmanouil
- Subjects
Male ,Medicin och hälsovetenskap ,Epidemiology ,VARIANTS ,Anthropometry/methods ,Body Height/genetics ,Body Mass Index ,Body Weight/genetics ,Body Weights and Measures ,Female ,Genetic Loci ,Genome, Human ,Genome-Wide Association Study ,Humans ,Polymorphism, Single Nucleotide ,Sex Characteristics ,Waist Circumference/genetics ,Waist-Hip Ratio ,Medical and Health Sciences ,ddc:576.5 ,GENETICS & HEREDITY ,ADULT HEIGHT ,RISK ,Anthropometry ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,OBESITY ,Genetic Epidemiology ,Medicine ,PPAR-GAMMA ,Waist Circumference ,Life Sciences & Biomedicine ,Medical Genetics ,Research Article ,VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 ,lcsh:QH426-470 ,515 Psychology ,education ,DIAGRAM Consortium ,Endocrinology and Diabetes ,VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714 ,MAGIC Investigators ,ddc:610 ,ENZYME-ACTIVITIES ,METAANALYSIS ,Medicinsk genetik ,0604 Genetics ,Science & Technology ,Body Weight ,FAT DISTRIBUTION ,Body Height ,BODY-MASS INDEX ,lcsh:Genetics ,3121 General medicine, internal medicine and other clinical medicine ,3111 Biomedicine ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,Developmental Biology - Abstract
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR, Author Summary Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
- Published
- 2013
14. Erratum: Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height ((The American Journal of Human Genetics (2010) 88 (6-18))
- Author
-
Lanktree, MB, Guo, Y, Murtaza, M, Glessner, JT, Bailey, SD, Onland-Moret, NC, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, CP, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, JS, Shah, S, Taylor, K, Barnard, J, Peters, BJ, Maloney, CM, Lobmeyer, MT, Stanton, A, Zafarmand, MH, Romaine, SPR, Mehta, A, Van Iperen, EPA, Gong, Y, Price, TS, Smith, EN, Kim, CE, Li, YR, Asselbergs, FW, Atwood, LD, Bailey, KM, Bhatt, D, Bauer, F, Behr, ER, Bhangale, T, Boer, JMA, Boehm, BO, Bradfield, JP, Brown, M, Braund, PS, Burton, PR, Carty, C, Chandrupatla, HR, Chen, W, Connell, J, Dalgeorgou, C, De Boer, A, Drenos, F, Elbers, CC, Fang, JC, Fox, CS, Frackelton, EC, Fuchs, B, Furlong, CE, Gibson, Q, Gieger, C, Goel, A, Grobbee, DE, Hastie, C, Howard, PJ, Huang, G-H, Johnson, WC, Li, Q, Kleber, ME, Klein, BEK, Klein, R, Kooperberg, C, Ky, B, Lacroix, A, Lanken, P, Lathrop, M, Li, M, Marshall, V, Melander, O, Mentch, FD, Meyer, NJ, Monda, KL, Montpetit, A, Murugesan, G, Nakayama, K, Nondahl, D, Onipinla, A, Rafelt, S, Newhouse, SJ, Otieno, FG, Patel, SR, Putt, ME, Rodriguez, S, Safa, RN, Sawyer, DB, Schreiner, PJ, Simpson, C, Sivapalaratnam, S, Srinivasan, SR, Suver, C, Swergold, G, Sweitzer, NK, Thomas, KA, Thorand, B, Timpson, NJ, Tischfield, S, Tobin, M, Tomaszewski, M, Verschuren, WMM, Wallace, C, Winkelmann, B, Zhang, H, Zheng, D, Zhang, L, Zmuda, JM, Clarke, R, Balmforth, AJ, Danesh, J, Day, IN, Schork, NJ, De Bakker, PIW, Delles, C, Duggan, D, Hingorani, AD, Hirschhorn, JN, Hofker, MH, Humphries, SE, Kivimaki, M, Lawlor, DA, Kottke-Marchant, K, Mega, JL, Mitchell, BD, Morrow, DA, Palmen, J, Redline, S, Shields, DC, Shuldiner, AR, Sleiman, PM, Smith, GD, Farrall, M, Jamshidi, Y, Christiani, DC, Casas, JP, Hall, AS, Doevendans, PA, Christie, JD, Berenson, GS, Murray, SS, Illig, T, Dorn, GW, Cappola, TP, Boerwinkle, E, Sever, P, Rader, DJ, Reilly, MP, Caulfield, M, Talmud, PJ, Topol, E, Engert, JC, Wang, K, Dominiczak, A, Hamsten, A, Curtis, SP, Silverstein, RL, Lange, LA, Sabatine, MS, Trip, M, Saleheen, D, Peden, JF, Cruickshanks, KJ, März, W, O'Connell, JR, Klungel, OH, Wijmenga, C, Maitland-Van Der Zee, AH, Schadt, EE, Johnson, JA, Jarvik, GP, Papanicolaou, GJ, Grant, SFA, Munroe, PB, North, KE, Samani, NJ, Koenig, W, Gaunt, TR, Anand, SS, Van Der Schouw, YT, Soranzo, N, Fitzgerald, GA, Reiner, A, Hegele, RA, Hakonarson, H, and Keating, BJ
- Published
- 2012
15. Erratum: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution (Nature Genetics (2010) 42 (949-960))
- Author
-
Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Vernon Smith, A, Visscher, PM, Yang, J, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, J-J, Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, MJ, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proença, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, M-L, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, J-O, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, SR, Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dörr, M, Elliott, P, Erdos, MR, Eriksson, JG, Freimer, NB, Fu, M, Gaget, S, Geus, EJC, Gjesing, AP, Grallert, H, Gräßler, J, Groves, CJ, Guiducci, C, Hartikainen, A-L, Hassanali, N, Havulinna, AS, Herzig, K-H, Hicks, AA, Hui, J, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, M-L, Luben, RN, Ludwig, B, McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Paré, G, Parker, AN, Peden, JF, Pichler, I, Pietiläinen, KH, Platou, CGP, Pouta, A, Ridderstråle, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, Van Meurs, JBJ, Van Ommen, G-J, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kähönen, M, Lehtimäki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, PM, Stumvoll, M, Tönjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H, Smith, GD, Ebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jørgensen, T, Karpe, F, Khaw, K-T, Laakso, M, Lawlor, DA, Marre, M, Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, JS, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, AT, Hofman, A, Hu, FB, Illig, T, Iribarren, C, Jarvelin, M-R, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, BW, Pramstaller, PP, Psaty, BM, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, TD, Syvanen, A-C, Uda, M, Uitterlinden, A, Völzke, H, Vollenweider, P, Wilson, JF, Witteman, JC, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, H-E, Thorsteinsdottir, U, Van Duijn, CM, Stefansson, K, Cupples, LA, Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL, and Lindgren, CM
- Published
- 2011
16. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
- Author
-
Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
- Subjects
Male ,Netherlands Twin Register (NTR) ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medizin ,Genome-wide association study ,Type 2 diabetes ,CORONARY HEART-DISEASE ,Fasting/blood ,0302 clinical medicine ,Insulin ,Glucose homeostasis ,ddc:576.5 ,Genome-wide ,Diabetes Mellitus, Type 2/blood/genetics/metabolism ,CARDIoGRAM Consortium ,POPULATION ,Proinsulin ,RISK ,Genetics ,0303 health sciences ,INSULIN SENSITIVITY ,11 Medical And Health Sciences ,Fasting ,Polymorphism, Single Nucleotide/genetics ,OBESITY ,Female ,type 2 diabetes ,Life Sciences & Biomedicine ,hormones, hormone substitutes, and hormone antagonists ,Insulin processing ,Adult ,medicine.medical_specialty ,endocrine system ,ENDOCRINOLOGY & METABOLISM ,SUSCEPTIBILITY LOCI ,Genotype ,030209 endocrinology & metabolism ,DIAGRAM Consortium ,Biology ,C4D Consortium ,Polymorphism, Single Nucleotide ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Insulin resistance ,BETA-CELL FUNCTION ,SDG 3 - Good Health and Well-being ,Internal medicine ,GIANT Consortium ,Internal Medicine ,medicine ,Humans ,METAANALYSIS ,030304 developmental biology ,Science & Technology ,Genome, Human ,Hormonal regulation [IGMD 6] ,Genetic Variation ,nutritional and metabolic diseases ,proinsulin ,medicine.disease ,Proinsulin/blood ,TCF7L2 ,Endocrinology ,Diabetes Mellitus, Type 2 ,MuTHER Consortium ,GLUCOSE-HOMEOSTASIS ,Insulin/blood - Abstract
OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
- Published
- 2011
17. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- Author
-
Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Mägi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, I, Steinthorsdottir, V, Stringham, H, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segrè, AV, Eestrada, K, Liang, L, Nemesh, J, Park, JH, Gustafsson, S, Kilpeläinen, TO, Yang, J, Bouatia-Naji, N, Eesko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, N, Goddard, ME, Heard-Costa, N, Hoesel, V, Hottenga, JJ, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, Van Wingerden, S, Watanabe, R, White, CC, and Wiklund, F
- Abstract
Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.
- Published
- 2010
18. Hundreds of variants clustered in genomic loci and biological pathways affect human height
- Author
-
Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segrè, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, JH, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Mägi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, JJ, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, and Pellikka, N
- Abstract
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P
- Published
- 2010
19. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci
- Author
-
Liu, CT, Monda, KL, Taylor, KC, Lange, L, Demerath, EW, Palmas, W, Wojczynski, MK, Ellis, JC, Vitolins, MZ, Liu, S, Papanicolaou, GJ, Irvin, MR, Xue, L, Griffin, PJ, Nalls, MA, Adeyemo, A, Liu, J, Li, G, Ruiz-Narvaez, EA, Chen, WM, Chen, F, Henderson, BE, Millikan, RC, Ambrosone, CB, Strom, SS, Guo, X, Andrews, JS, Sun, YV, Mosley, TH, Yanek, LR, Shriner, D, Haritunians, T, Rotter, JI, Speliotes, EK, Smith, M, Rosenberg, L, Mychaleckyj, J, Nayak, U, Spruill, I, Garvey, WT, Pettaway, C, Nyante, S, Bandera, EV, Britton, AF, Zonderman, AB, Rasmussen-Torvik, LJ, Chen, YDI, Ding, J, Lohman, K, Kritchevsky, SB, Zhao, W, Peyser, PA, Kardia, SLR, Kabagambe, E, Broeckel, U, Chen, G, Zhou, J, Wassertheil-Smoller, S, Neuhouser, ML, Rampersaud, E, Psaty, B, Kooperberg, C, Manson, JAE, Kuller, LH, Ochs-Balcom, HM, Johnson, KC, Sucheston, L, Ordovas, JM, Palmer, JR, Haiman, CA, McKnight, B, Howard, BV, Becker, DM, Bielak, LF, Liu, Y, Allison, MA, Grant, SFA, Burke, GL, Patel, SR, Schreiner, PJ, Borecki, IB, Evans, MK, Taylor, H, Sale, MM, Howard, V, Carlson, CS, Rotimi, CN, Cushman, M, Harris, TB, Reiner, AP, Cupples, LA, North, KE, Fox, CS, Liu, CT, Monda, KL, Taylor, KC, Lange, L, Demerath, EW, Palmas, W, Wojczynski, MK, Ellis, JC, Vitolins, MZ, Liu, S, Papanicolaou, GJ, Irvin, MR, Xue, L, Griffin, PJ, Nalls, MA, Adeyemo, A, Liu, J, Li, G, Ruiz-Narvaez, EA, Chen, WM, Chen, F, Henderson, BE, Millikan, RC, Ambrosone, CB, Strom, SS, Guo, X, Andrews, JS, Sun, YV, Mosley, TH, Yanek, LR, Shriner, D, Haritunians, T, Rotter, JI, Speliotes, EK, Smith, M, Rosenberg, L, Mychaleckyj, J, Nayak, U, Spruill, I, Garvey, WT, Pettaway, C, Nyante, S, Bandera, EV, Britton, AF, Zonderman, AB, Rasmussen-Torvik, LJ, Chen, YDI, Ding, J, Lohman, K, Kritchevsky, SB, Zhao, W, Peyser, PA, Kardia, SLR, Kabagambe, E, Broeckel, U, Chen, G, Zhou, J, Wassertheil-Smoller, S, Neuhouser, ML, Rampersaud, E, Psaty, B, Kooperberg, C, Manson, JAE, Kuller, LH, Ochs-Balcom, HM, Johnson, KC, Sucheston, L, Ordovas, JM, Palmer, JR, Haiman, CA, McKnight, B, Howard, BV, Becker, DM, Bielak, LF, Liu, Y, Allison, MA, Grant, SFA, Burke, GL, Patel, SR, Schreiner, PJ, Borecki, IB, Evans, MK, Taylor, H, Sale, MM, Howard, V, Carlson, CS, Rotimi, CN, Cushman, M, Harris, TB, Reiner, AP, Cupples, LA, North, KE, and Fox, CS
- Abstract
Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10-6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10-8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10-8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10-8; RREB1: p = 5.7×10-8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distr
- Published
- 2013
20. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
-
Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., BRAMBILLA, PAOLO, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., and BRAMBILLA, PAOLO
- Abstract
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
- Published
- 2013
21. Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children
- Author
-
Kilpelainen, TO, Qi, L, Brage, S, Sharp, SJ, Sonestedt, E, Demerath, E, Ahmad, T, Mora, S, Kaakinen, M, Sandholt, CH, Holzapfel, C, Autenrieth, CS, Hypponen, E, Cauchi, S, He, MA, Kutalik, Z, Kumari, M, Stancakova, A, Meidtner, K, Balkau, B, Tan, JT, Mangino, M, Timpson, NJ, Song, YQ, Zillikens, M.C., Jablonski, KA, Garcia, ME, Johansson, S, Bragg-Gresham, JL, Wu, Fenny, van Vliet-Ostaptchouk, JV, Onland-Moret, NC, Zimmermann, E, Rivera, NV, Tanaka, T, Stringham, HM, Silbernagel, G, Kanoni, S, Feitosa, MF, Snitker, S, Ruiz, JR, Metter, J, Larrad, MTM, Atalay, M, Hakanen, M, Amin, Najaf, Cavalcanti-Proenca, C, Grontved, A, Hallmans, G, Jansson, JO, Kuusisto, J, Kahonen, M, Lutsey, PL, Nolan, JJ, Palla, L, Pedersen, O, Perusse, L, Renstrom, F, Scott, RA, Shungin, D, Sovio, U, Tammelin, TH, Ronnemaa, T, Lakka, TA, Uusitupa, M, Rios, MS, Ferrucci, L, Bouchard, C, Meirhaeghe, A, Fu, M, Walker, M, Borecki, IB, Dedoussis, GV, Fritsche, A, Ohlsson, C, Boehnke, M, Bandinelli, S, Duijn, Cornelia, Ebrahim, S, Lawlor, DA, Gudnason, V, Harris, TB, Sorensen, TIA, Mohlke, KL, Hofman, Bert, Uitterlinden, André, Tuomilehto, J, Lehtimaki, T, Raitakari, O, Isomaa, B, Njolstad, PR, Florez, JC, Liu, SM (Simin), Ness, A, Spector, TD, Tai, ES, Froguel, P, Boeing, H, Laakso, M, Marmot, M, Bergmann, S, Power, C, Khaw, KT, Chasman, D, Ridker, P, Hansen, T, Monda, KL, Illig, T, Jarvelin, MR, Wareham, NJ, Hu, FB, Groop, LC, Orho-Melander, M, Ekelund, U, Franks, PW, Loos, RJF, Kilpelainen, TO, Qi, L, Brage, S, Sharp, SJ, Sonestedt, E, Demerath, E, Ahmad, T, Mora, S, Kaakinen, M, Sandholt, CH, Holzapfel, C, Autenrieth, CS, Hypponen, E, Cauchi, S, He, MA, Kutalik, Z, Kumari, M, Stancakova, A, Meidtner, K, Balkau, B, Tan, JT, Mangino, M, Timpson, NJ, Song, YQ, Zillikens, M.C., Jablonski, KA, Garcia, ME, Johansson, S, Bragg-Gresham, JL, Wu, Fenny, van Vliet-Ostaptchouk, JV, Onland-Moret, NC, Zimmermann, E, Rivera, NV, Tanaka, T, Stringham, HM, Silbernagel, G, Kanoni, S, Feitosa, MF, Snitker, S, Ruiz, JR, Metter, J, Larrad, MTM, Atalay, M, Hakanen, M, Amin, Najaf, Cavalcanti-Proenca, C, Grontved, A, Hallmans, G, Jansson, JO, Kuusisto, J, Kahonen, M, Lutsey, PL, Nolan, JJ, Palla, L, Pedersen, O, Perusse, L, Renstrom, F, Scott, RA, Shungin, D, Sovio, U, Tammelin, TH, Ronnemaa, T, Lakka, TA, Uusitupa, M, Rios, MS, Ferrucci, L, Bouchard, C, Meirhaeghe, A, Fu, M, Walker, M, Borecki, IB, Dedoussis, GV, Fritsche, A, Ohlsson, C, Boehnke, M, Bandinelli, S, Duijn, Cornelia, Ebrahim, S, Lawlor, DA, Gudnason, V, Harris, TB, Sorensen, TIA, Mohlke, KL, Hofman, Bert, Uitterlinden, André, Tuomilehto, J, Lehtimaki, T, Raitakari, O, Isomaa, B, Njolstad, PR, Florez, JC, Liu, SM (Simin), Ness, A, Spector, TD, Tai, ES, Froguel, P, Boeing, H, Laakso, M, Marmot, M, Bergmann, S, Power, C, Khaw, KT, Chasman, D, Ridker, P, Hansen, T, Monda, KL, Illig, T, Jarvelin, MR, Wareham, NJ, Hu, FB, Groop, LC, Orho-Melander, M, Ekelund, U, Franks, PW, and Loos, RJF
- Abstract
Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
- Published
- 2011
22. NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium
- Author
-
Heard-Costa, NL, Zillikens, M.C., Monda, KL, Johansson, A, Harris, TB, Fu, M, Haritunians, T, Feitosa, MF, Aspelund, T, Eiriksdottir, G, Garcia, M, Launer, LJ (Lenore), Smith, AV, Mitchell, BD, McArdle, PF, Shuldiner, AR, Bielinski, SJ, Boerwinkle, E, Brancati, F, Demerath, EW, Pankow, JS, Arnold, AM, Chen, YDI, Glazer, NL, McKnight, B, Psaty, BM, Rotter, JI, Amin, Najaf, Campbell, H, Gyllensten, U, Pattaro, C, Pramstaller, PP, Rudan, I, Struchalin, Maksim, Vitart, V, Gao, XY, Kraja, A, Province, MA, Zhang, QY, Atwood, LD, Dupuis, J, Hirschhorn, JN, Jaquish, CE, O'Donnell, CJ, Vasan, RS, White, CC, Aulchenko, YS, Estrada Gil, Karol, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Witteman, JCM, Oostra, Ben, Kaplan, RC, Gudnason, V, O'Connell, JR, Borecki, IB, Duijn, Cornelia, Cupples, LA, Fox, CS, North, KE, Heard-Costa, NL, Zillikens, M.C., Monda, KL, Johansson, A, Harris, TB, Fu, M, Haritunians, T, Feitosa, MF, Aspelund, T, Eiriksdottir, G, Garcia, M, Launer, LJ (Lenore), Smith, AV, Mitchell, BD, McArdle, PF, Shuldiner, AR, Bielinski, SJ, Boerwinkle, E, Brancati, F, Demerath, EW, Pankow, JS, Arnold, AM, Chen, YDI, Glazer, NL, McKnight, B, Psaty, BM, Rotter, JI, Amin, Najaf, Campbell, H, Gyllensten, U, Pattaro, C, Pramstaller, PP, Rudan, I, Struchalin, Maksim, Vitart, V, Gao, XY, Kraja, A, Province, MA, Zhang, QY, Atwood, LD, Dupuis, J, Hirschhorn, JN, Jaquish, CE, O'Donnell, CJ, Vasan, RS, White, CC, Aulchenko, YS, Estrada Gil, Karol, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Witteman, JCM, Oostra, Ben, Kaplan, RC, Gudnason, V, O'Connell, JR, Borecki, IB, Duijn, Cornelia, Cupples, LA, Fox, CS, and North, KE
- Abstract
Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4x10(-7))]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3x10(-8) for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4x10(-6), 0.024 z-score units (0.10 kg/m(2)) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07-1.19; p = 3.2x10(-5) per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
- Published
- 2009
23. Fat mass and obesity gene and cognitive decline: the Atherosclerosis Risk in Communities Study.
- Author
-
Bressler J, Fornage M, Demerath EW, Knopman DS, Monda KL, North KE, Penman A, Mosley TH, Boerwinkle E, Bressler, Jan, Fornage, Myriam, Demerath, Ellen W, Knopman, David S, Monda, Keri L, North, Kari E, Penman, Alan, Mosley, Thomas H, and Boerwinkle, Eric
- Published
- 2013
- Full Text
- View/download PDF
24. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- Author
-
Zhaoming Wang, André Scherag, James F. Wilson, Nancy L. Heard-Costa, Ingrid B. Borecki, Sang Hong Lee, Veronique Vitart, Zoltán Kutalik, Jeffrey R. O'Connell, Mieke D. Trip, Lu Qi, Peter Vollenweider, Jennifer L. Bragg-Gresham, Davide Gentilini, Kees Hovingh, Lynda M. Rose, Carolin Pütter, Martin Farrall, Albert V. Smith, Nicholas G. Martin, Tõnu Esko, David J. Hunter, Georg Homuth, Liming Liang, Yudi Pawitan, Winfried März, George Dedoussis, Irene Mateo Leach, Nicholas J. Wareham, Lars Lind, Thomas Illig, Andrew P. Morris, Daniele Cusi, Jouke-Jan Hottenga, Tove Fall, Themistocles L. Assimes, Massimo Mangino, Dmitry Shungin, Kari Stefansson, Anne U. Jackson, Inês Barroso, Sarah E. Medland, Lude Franke, Karen L. Mohlke, Folkert W. Asselbergs, Sarah E. Hunt, Gudmar Thorleifsson, Pablo V. Gejman, Serena Sanna, Mark I. McCarthy, David M. Evans, Joel N. Hirschhorn, Alan F. Wright, Sarah H. Wild, Patricia B. Munroe, Marcel Bruinenberg, Gonneke Willemsen, Ulf de Faire, Markku Laakso, Marja-Liisa Lokki, Andrew C. Heath, Jing Hua Zhao, Lavinia Paternoster, Jana V. van Vliet-Ostaptchouk, Sailaja Vedantam, Danyu Lin, Eric E. Schadt, Stefano Signorini, Harald Grallert, Tsegaselassie Workalemahu, Jonathan Tyrer, Albert Hofman, George Nicholson, Patrik K. E. Magnusson, Arthur W. Musk, Jian Yang, Vilmundur Gudnason, Robert C. Kaplan, Panos Deloukas, Nilesh J. Samani, Inke R. König, Frank B. Hu, Paul M. Ridker, Tamara B. Harris, Bruce H. R. Wolffenbuttel, Ellen A. Nohr, Sarah Edkins, Lambertus A. Kiemeney, Anke Hinney, Eric Boerwinkle, Klaus Stark, Ben A. Oostra, Barbara Thorand, Unnur Thorsteinsdottir, Meena Kumari, Evelin Mihailov, Caroline S. Fox, Michael Boehnke, Aroon D. Hingorani, Jonathan Stephens, Kathleen Stirrups, Inga Prokopenko, Anke Tönjes, Lili Milani, John Beilby, Carlos Iribarren, Kari E. North, Cécile Lecoeur, So-Youn Shin, Marjo-Riitta Järvelin, Matti Uusitupa, Åsa Johansson, Nancy L. Pedersen, Krista Fischer, Fernando Rivadeneira, Wolfgang Koenig, Fredrik Karpe, Antti Jula, Lindsay L. Waite, Gérard Waeber, Mustafa Atalay, Heribert Schunkert, Narisu Narisu, Sita H. Vermeulen, Bernhard R. Winkelmann, Guo Li, Anders Hamsten, Elizabeth K. Speliotes, Ivonne Jarick, Sirkka Keinänen-Kiukaanniemi, L. Adrienne Cupples, Ruth J. F. Loos, Martina Müller-Nurasyid, David-Alexandre Trégouët, Claudia Langenberg, Willem H. Ouwehand, Julius S. Ngwa, Jennifer E. Huffman, H-Erich Wichmann, Amy J. Swift, Marco M Ferrario, Leif Groop, Henrik Grönberg, Peter M. Visscher, Claes Ohlsson, Markku S. Nieminen, Aparna Radhakrishnan, Harold Snieder, Devin Absher, Albertine J. Oldehinkel, Erik Ingelsson, Anna Maria Di Blasio, M. Carola Zillikens, Veikko Salomaa, Colin N. A. Palmer, Lori L. Bonnycastle, Teresa Ferreira, Ronald P. Stolk, Annette Peters, Philippe Froguel, Michael Stumvoll, David Schlessinger, Maria Dimitriou, Timo Saaristo, Cristen J. Willer, Jarmo Virtamo, Jorma Viikari, Alena Stančáková, Mika Kivimäki, Paolo Brambilla, Jaakko Tuomilehto, Dorret I. Boomsma, Harry Campbell, Jianjun Liu, Daniel I. Chasman, Gonçalo R. Abecasis, Ilja M. Nolte, Karl-Heinz Jöckel, Reedik Mägi, Pamela A. F. Madden, Jaana Laitinen, Sonja I. Berndt, Frank Kee, Marcus E. Kleber, Jacqueline C.M. Witteman, Jouko Saramies, Francis S. Collins, Johan G. Eriksson, Melanie M. van der Klauw, Yi-Juan Hu, John F. Peden, Markus Perola, Henri Wallaschofski, Jean Ferrières, Elena Tremoli, Marjolein J. Peters, Olli T. Raitakari, Claudia Lamina, Sekar Kathiresan, Mary F. Feitosa, Diana Kuh, Tim D. Spector, Paul W. Franks, Gerjan Navis, Martin den Heijer, Christian Gieger, Kevin B. Jacobs, Andrea Ganna, Timothy M. Frayling, Iris M. Heid, Bernhard O. Boehm, Eleanor Wheeler, Sonali Pechlivanis, Miriam F. Moffatt, Brenda W.J.H. Penninx, Anna-Liisa Hartikainen, Augusto Rendon, Stefan Schreiber, Stephen J. Chanock, Andrew R. Wood, Jianxin Shi, Najaf Amin, Lenore J. Launer, Michael A. Province, Jeanette Erdmann, Mattias Lorentzon, Hugh Watkins, Johanna Kuusisto, John-Olov Jansson, David P. Strachan, Anne E. Justice, Toby Johnson, Cornelia M. van Duijn, Niina Eklund, Samuli Ripatti, Aarno Palotie, Aldi T. Kraja, Michael Preuss, Rona J. Strawbridge, Ozren Polasek, Elisabeth Widen, Barbara McKnight, Mariano Dei, Vincent Mooser, Josine L. Min, Caroline Hayward, Mika Kähönen, Peter P. Pramstaller, Femmie de Vegt, Rainer Rauramaa, Douglas F. Levinson, Diana Marek, Antonio Liuzzi, Stefan Gustafsson, Andrew A. Hicks, Gemma Cadby, Damien C. Croteau-Chonka, Mark J. Caulfield, Boris Skrobek, Lyle J. Palmer, Alexander Teumer, Ken K. Ong, Ulf Gyllensten, Anneli Pouta, Anuj Goel, Eva Albrecht, Kristian Hveem, Inger Njølstad, David Meyre, Ida Surakka, Francesca Frau, Paolo Manunta, Sabine Schipf, Carolina Medina-Gomez, Kay-Tee Khaw, Alan R. Sanders, Thorkild I. A. Sørensen, André G. Uitterlinden, Alistair S. Hall, Felix R. Day, Karol Estrada, Jennifer G. Sambrook, Eirini V. Theodoraki, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Talin Haritunian, Benjamin M. Neale, Juha Sinisalo, Kati Kristiansson, Thomas W. Winkler, Pim van der Harst, Peter S. Chines, Joyce B. J. van Meurs, Wendy L. McArdle, Andrew Wong, Grant W. Montgomery, Terho Lehtimäki, Igor Rudan, Keri L. Monda, John M. C. Connell, Jian'an Luan, Per Hall, Joshua C. Randall, Anthony J. Balmforth, Chris Power, Philippe Amouyel, Andres Metspalu, Johannes Hebebrand, Andrew D. Morris, Jaana Lindström, Liesbeth Vandenput, William O.C.M. Cookson, Hanneke Basart, Stavroula Kanoni, Elina Hyppönen, Christian Hengstenberg, Thomas W. Mühleisen, Kari Kuulasmaa, Timo A. Lakka, Nicole Soranzo, Bruce M. Psaty, Antony P. Attwood, Epidemiology, Clinical Genetics, Surgery, Erasmus School of Social and Behavioural Sciences, Public Health, Internal Medicine, Immunology, Child and Adolescent Psychiatry / Psychology, Internal medicine, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Other departments, Vascular Medicine, Biological Psychology, Cognitive Psychology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Life Course Epidemiology (LCE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Medical Research Council (MRC), Berndt, Sonja I, Gustafsson, Stefan, Mägi, Reedik, Ganna, Andrea, Lee, Sang Hong, Hyppönen, Elina Tuulikki, Ingelsson, Erik, Berndt, Si, Feitosa, Mf, Justice, Ae, Monda, Kl, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Randall, Jc, Willer, Cj, Winkler, Tw, Wood, Ar, Hu, Yj, Lee, Sh, Lin, Dy, Min, Jl, Neale, Bm, BRAGG GRESHAM, Jl, DEN HEIJER, M, Hottenga, Jj, Huffman, Je, Johansson, A, Kleber, Me, König, Ir, Mcardle, Wl, MEDINA GOMEZ, C, MÜLLER NURASYID, M, Nolte, Im, Peters, Mj, Rose, Lm, Smith, Av, Strawbridge, Rj, Trip, Md, VAN VLIET OSTAPTCHOUK, Jv, Waite, Ll, Zhao, Jh, Asselbergs, Fw, Attwood, Ap, Balmforth, Aj, Bonnycastle, Ll, Chasman, Di, Connell, Jm, Cookson, Wo, DE FAIRE, U, DE VEGT, F, Evans, Dm, Ferrario, Mm, Gejman, Pv, Hartikainen, Al, HEARD COSTA, Nl, Heath, Ac, Hu, Fb, Hunt, Se, Jacobs, Kb, Jansson, Jo, Khaw, Kt, Kraja, At, Laitinen, Jh, Lakka, Ta, Launer, Lj, Lokki, Ml, Madden, Pa, Magnusson, Pk, Manunta, Paolo, MATEO LEACH, I, Medland, Se, Montgomery, Gw, Mühleisen, Tw, Munroe, Pb, Musk, Aw, Nohr, Ea, Ong, Kk, Oostra, Ba, Palmer, Cn, Peden, Jf, Pramstaller, Pp, Saaristo, Te, Sambrook, Jg, Sanders, Ar, Shin, Sy, Stephens, Jc, Stolk, Rp, Swift, Aj, Theodoraki, Ev, Tregouet, Da, VAN DER KLAUW, Mm, VAN MEURS, Jb, Vermeulen, Sh, Wild, Sh, Winkelmann, Br, Witteman, Jc, Wolffenbuttel, Bh, Wright, Af, Zillikens, Mc, Boehm, Bo, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Cupples, La, Dedoussis, Gv, Eriksson, Jg, Franks, Pw, Harris, Tb, Hicks, Aa, Hovingh, Kg, Jarvelin, Mr, Jöckel, Kh, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Levinson, Df, Martin, Ng, Morris, Ad, Oldehinkel, Aj, Ouwehand, Wh, Palmer, Lj, Province, Ma, Psaty, Bm, Ridker, Pm, Samani, Nj, Sørensen, Ti, Spector, Td, Uitterlinden, Ag, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Abecasis, Gr, Assimes, Tl, Borecki, Ib, Groop, Lc, Heid, Im, Kaplan, Rc, Moffatt, Mf, Mohlke, Kl, O'Connell, Jr, Schadt, Ee, Strachan, Dp, VAN DUIJN, Cm, Visscher, Pm, DI BLASIO, Am, Hirschhorn, Jn, Lindgren, Cm, Morris, Ap, Mccarthy, Mi, Speliotes, Ek, North, Ke, Loos, Rj, and Ingelsson, E.
- Subjects
Netherlands Twin Register (NTR) ,Linkage disequilibrium ,SORTILIN ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Medizin ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,polymorphism ,Body Mass Index ,0302 clinical medicine ,Missing heritability problem ,MISSING HERITABILITY ,EXTREME OBESITY ,CONFER RISK ,POPULATION ,Genetics & Heredity ,2. Zero hunger ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,Anthropometry ,COMMON VARIANTS ,Single Nucleotide ,ASSOCIATION ,Biological Sciences ,Anthropometry, Body Height ,genetics, Body Mass Index, Case-Control Studies, European Continental Ancestry Group ,genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity ,genetics, Phenotype, Polymorphism ,genetics, Quantitative Trait Loci, Waist-Hip Ratio ,Phenotype ,Life Sciences & Biomedicine ,EXPRESSION ,Genotype ,Missing heritabillity ,Population ,European Continental Ancestry Group ,Quantitative Trait Loci ,EARLY-ONSET ,Genomics ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Article ,White People ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Meta-Analysis as Topic ,SDG 3 - Good Health and Well-being ,Humans ,Genetic Predisposition to Disease ,Obesity ,body height/genetics ,Polymorphism ,Allele ,Genetik ,education ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,030304 developmental biology ,Science & Technology ,Waist-Hip Ratio ,BMI, height, WHR, obesity, GWS ,ta3121 ,Genetic architecture ,Body Height ,BODY-MASS INDEX ,Case-Control Studies ,gene ,stature ,height ,030217 neurology & neurosurgery ,Developmental Biology ,Genome-Wide Association Study - Abstract
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups. © 2013 Nature America, Inc. All rights reserved.
- Published
- 2013
25. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- Author
-
Fredrik Karpe, Ivonne Jarick, Julius S. Ngwa, Alan F. Wright, Robert Luben, Aaron R. Folsom, Sailaja Vedantam, Veikko Salomaa, Markku J. Savolainen, Robert Clarke, Shah Ebrahim, Thomas A. Buchanan, Mao Fu, Albert Hofman, Philippe Goyette, Camilla H. Sandholt, Fabio Macciardi, Elizabeth K. Speliotes, Barbara McKnight, Anne McCarthy, Mika Kaehoenen, Christian Gieger, Jorma S. A. Viikari, Nicholas J. Timpson, Kirsti Kvaløy, Douglas F. Levinson, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Andrew A. Hicks, Niina Pellikka, Charles C. White, Leena Peltonen, Reedik Maegi, John-Olov Jansson, Qunyuan Zhang, Claudia Lamina, Robert C. Kaplan, Peter M. Visscher, Laura J. Scott, Claes Ohlsson, Brian Thomson, Jubao Duan, Heikki V. Huikuri, Stephen O'Rahilly, Anette P. Gjesing, David P. Strachan, Caroline S. Fox, Sekar Kathiresan, Anna-Liisa Hartikainen, Johannes Kettunen, Maris Teder-Laving, Erik Ingelsson, Mario A. Morken, Peter Kovacs, Elisabeth Widen, Caroline Hayward, Eleanor Wheeler, Jing Hua Zhao, Vilmundur Gudnason, Panos Deloukas, Jacqueline C. M. Witteman, Gert-Jan B. van Ommen, Eric Boerwinkle, Martin Wabitsch, Christian Hengstenberg, Beverley Balkau, Thor Aspelund, Neelam Hassanali, Paul M. Ridker, Nicole L. Glazer, Joyce B. J. van Meurs, Michel Marre, Alan James, Ben A. Oostra, David Meyre, Ida Surakka, Stefan Schreiber, Nigel W. Rayner, Heribert Schunkert, Thomas Quertermous, Stefan Gustafsson, Peter Kraft, Benjamin F. Voight, Irene Pichler, Olle Melander, Ozren Polasek, Antti Jula, Alan R. Sanders, Andrew R. Wood, Yoav Ben-Shlomo, Thomas Illig, Jianjun Liu, Gerard Waeber, André G. Uitterlinden, Torben Hansen, Helene Alavere, André Scherag, Paolo Manunta, Johannes Hebebrand, Themistocles L. Assimes, Stefan R. Bornstein, Jaakko Tuomilehto, Morris Brown, Jianfeng Xu, Yii-Der Ida Chen, Nancy L. Heard-Costa, Cristen J. Willer, Henrik Greonberg, Guillaume Lettre, John R. Thompson, Inês Barroso, John R. B. Perry, Andreas Ziegler, James F. Wilson, Christopher J. O'Donnell, Maurizio F. Facheris, Robert Lawrence, Jan Smit, Lyle J. Palmer, Ulf Gyllensten, Richard B. Hayes, Shengxu Li, Barbara Ludwig, Larry D. Atwood, Valgerdur Steinthorsdottir, Sabine Schipf, Jouko Saramies, Tanja Boes, Martin Ridderstråle, Jennie Hui, Lina Zgaga, Susann Scherag, Alexandra I. F. Blakemore, Marjolein Peters, Timo T. Valle, Nelson B. Freimer, Kay-Tee Khaw, Amy J. Swift, Michael Stumvoll, Miriam F. Moffatt, Cecilia M. Lindgren, Ayellet V. Segrè, Neil Robertson, Richard N. Bergman, Francis S. Collins, Ryan P. Welch, Mari-Liis Tammesoo, Devin Absher, Tamara B. Harris, Kari E. North, Manuela Uda, Karen L. Mohlke, Inga Prokopenko, Per Hall, Gudmar Thorleifsson, Marjo-Riitta Järvelin, Guillaume Paré, Stefan Gaget, G. Bragi Walters, Michael N. Weedon, Jean-Claude Tardif, Mary F. Feitosa, Anke Toenjes, Ken K. Ong, Cécile Lecoeur, Paavo Zitting, David S. Siscovick, Chih-Mei Chen, Peter Almgren, Anneli Pouta, Philippe Froguel, Pekka Jousilahti, Jaakko Kaprio, Maria Teresa Sciarrone Alibrandi, Sophie van Wingerden, Steven A. McCarroll, Oluf Pedersen, Shaun Purcell, Veronique Vitart, Leena Kinnunen, Markus Perola, Jacques S. Beckmann, Vincent Vatin, Christopher J. Groves, Zoltán Kutalik, Lu Qi, Volker Hoesel, Seppo Koskinen, Suzanne Rafelt, Anke Hinney, Annette Peters, David Schlessinger, Eero Kajantie, Jian Yang, Nicholas G. Martin, Joshua W. Knowles, Kristian Midthjell, Olivier Lantieri, Dorret I. Boomsma, Harry Campbell, Ulrich John, Kirsi H. Pietilaeinen, George Davey Smith, Carl G. P. Platou, Sarah H. Wild, Patricia B. Munroe, Iris M. Heid, Diana Marek, Michael Boehnke, Andres Metspalu, Hana Lango Allen, Peter Rzehak, Christine Cavalcanti-Proença, M. Carola Zillikens, Åsa Johansson, Anuj Goel, Andrew T. Hattersley, Massimo Mangino, Michael E. Goddard, Tim D. Spector, Winfried Rief, Jonathan Tyrer, Lachlan J. M. Coin, Peter P. Pramstaller, Narisu Narisu, John Beilby, Jonathan Stephens, Christina Barlassina, Pamela Fischer-Posovszky, Brenda W.J.H. Penninx, Kaisa Silander, Richard H. Myers, Jouke-Jan Hottenga, Eric E. Schadt, Francesco P. Cappuccio, Martin den Heijer, Fernando Rivadeneira, Lindsay L. Waite, Wilmar Igl, Igor Rudan, Manjinder S. Sandhu, Debbie A Lawlor, Kristian Hveem, Susanna Wiegand, Mari Nelis, Thomas Reinehr, Elisabeth Thiering, Inke R. Koenig, Stephan B. Felix, Fredrik Wiklund, Ian N. M. Day, Willem H. Ouwehand, Peter Schwarz, Richard M. Watanabe, Keri L. Monda, Kari Stefansson, Gudny Eiriksdottir, H-Erich Wichmann, Jianxin Shi, Najaf Amin, Carlos Iribarren, Heiko Krude, Dale R. Nyholt, Lenore J. Launer, Stephen J. Chanock, Harald Grallert, Hugh Watkins, Juergen Graessler, Tsegaselassie Workalemahu, Jeanette Erdmann, Mattias Lorentzon, Leif Groop, Teresa Ferreira, Chiara Lanzani, Johanna Kuusisto, Johan G. Eriksson, Tõnu Esko, Torben Jørgensen, Robert J. Weyant, Michael Preuss, Lambertus A. Kiemeney, Daniel I. Chasman, Daniel R. Witte, Kevin B. Jacobs, Nicole Soranzo, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Joachim Heinrich, Anthony J. Balmforth, Eva Fisher, Elizabeth S. Jewell, Alice M. Arnold, Nele Friedrich, Olli T. Raitakari, Henri Wallaschofski, Jeffrey R. O'Connell, Terho Lehtimaeki, Marika Kaakinen, Heather M. Stringham, Bo Isomaa, I. Sadaf Farooqi, Anna L. Dixon, Anne U. Jackson, Mark I. McCarthy, Lori L. Bonnycastle, Aila Rissanen, Joel N. Hirschhorn, Nilesh J. Samani, Aimo Ruokonen, Frank B. Hu, L. Adrienne Cupples, Amanda J. Bennett, Shamika Ketkar, Ruth J. F. Loos, Nicholas J. Wareham, Tiinamaija Tuomi, Timothy M. Frayling, Ulla Sovio, Georg Homuth, Liming Liang, Heiner Boeing, Unnur Thorsteinsdottir, Ingrid B. Borecki, Danielle M. Greenawalt, Rosanda Mulić, Ivana Kolcic, Talin Haritunians, Mark J. Caulfield, Marja-Liisa Lokki, Tanya M. Teslovich, Paul Elliott, Matt Neville, Nilanjan Chatterjee, Albert V. Smith, Andrew P. Morris, Fabio Busonero, Gonçalo R. Abecasis, Jaana Laitinen, Michael R. Erdos, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Pablo V. Gejman, Alan R. Shuldiner, Serena Sanna, David J. Hunter, Sonja I. Berndt, Carla I. G. Vogel, Alistair S. Hall, Karol Estrada, Sven Bergmann, Thomas Meitinger, Gonneke Willemsen, Andrew C. Heath, Katja K.H. Aben, Markku Laakso, Juha Sinisalo, Tuomas O. Kilpelaenen, Mark E. Cooper, Heike Biebermann, Eco J. C. de Geus, Grant W. Montgomery, Sophie Visvikis-Siest, Thomas W. Winkler, Ju-Hyun Park, Alex N. Parker, Peter S. Chines, James Nemesh, Nabila Bouatia-Naji, Wendy L. McArdle, Roberto Elosua, Markku S. Nieminen, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Epidemiology, Internal Medicine, Clinical Genetics, Radiology & Nuclear Medicine, Erasmus MC other, Public Health, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, MAGIC, Procardis Consortium, Medical Research Council (MRC), Speliotes, Ek, Willer, Cj, Berndt, Si, Monda, Kl, Thorleifsson, G, Jackson, Au, Allen, Hl, Lindgren, Cm, Luan, J, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Qi, L, Workalemahu, T, Heid, Im, Steinthorsdottir, V, Stringham, Hm, Weedon, Mn, Wheeler, E, Wood, Ar, Ferreira, T, Weyant, Rj, Segrè, Av, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Gustafsson, S, Kilpeläinen, To, Yang, J, BOUATIA NAJI, N, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Amin, N, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, HEARD COSTA, Nl, Hoesel, V, Hottenga, Jj, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Narisu, N, Perry, Jr, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, Lj, Timpson, Nj, Tyrer, Jp, VAN WINGERDEN, S, Watanabe, Rm, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Almgren, P, Arnold, Am, Aspelund, T, Atwood, Ld, Balkau, B, Balmforth, Aj, Bennett, Aj, BEN SHLOMO, Y, Bergman, Rn, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bonnycastle, Ll, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Campbell, H, Cappuccio, Fp, CAVALCANTI PROENÇA, C, Chen, Yd, Chen, Cm, Chines, P, Clarke, R, Coin, L, Connell, J, Day, In, DEN HEIJER, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, Mr, Eriksson, Jg, Facheris, Mf, Felix, Sb, FISCHER POSOVSZKY, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gieger, C, Gjesing, Ap, Goel, A, Goyette, P, Grallert, H, Grässler, J, Greenawalt, Dm, Groves, Cj, Gudnason, V, Guiducci, C, Hartikainen, Al, Hassanali, N, Hall, A, Havulinna, A, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Lehtimäki, T, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, Paolo, Marek, D, Marre, M, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, Gw, Morken, Ma, Morris, Ap, Mulic, R, Ngwa, J, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Robertson, Nr, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, M, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, D, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, Aj, Tammesoo, Ml, Tardif, Jc, TEDER LAVING, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, Tuomi, T, VAN MEURS, Jb, VAN OMMEN, Gj, Vatin, V, Viikari, J, VISVIKIS SIEST, S, Vitart, V, Vogel, Ci, Voight, Bf, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, I, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, M, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, J, Boeing, H, Boerwinkle, E, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Collins, F, Cupples, La, Smith, Gd, Erdmann, J, Froguel, P, Grönberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, Tb, Hattersley, At, Hayes, Rb, Heinrich, J, Hu, Fb, Hveem, K, Illig, T, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Laakso, M, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Pedersen, O, Penninx, Bw, Peters, A, Pramstaller, Pp, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, Tt, Wabitsch, M, Waeber, G, Wareham, Nj, Watkins, H, Procardis, Consortium, Wilson, Jf, Wright, Af, Zillikens, Mc, Chatterjee, N, Mccarroll, Sa, Purcell, S, Schadt, Ee, Visscher, Pm, Assimes, Tl, Borecki, Ib, Deloukas, P, Fox, C, Groop, Lc, Haritunians, T, Hunter, Dj, Kaplan, Rc, Mohlke, Kl, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, VAN DUIJN, Cm, Wichmann, He, Frayling, Tm, Thorsteinsdottir, U, Abecasis, Gr, Barroso, I, Boehnke, M, Stefansson, K, North, Ke, Mccarthy, Mi, Hirschhorn, Jn, Ingelsson, E, and Loos, Rj
- Subjects
Netherlands Twin Register (NTR) ,Medizin ,Genome-wide association study ,Aetiology, screening and detection [ONCOL 5] ,FTO gene ,Body Mass Index ,0302 clinical medicine ,SH2B1 ,GASTRIC-INHIBITORY POLYPEPTIDE ,ADULT OBESITY ,Glucose homeostasis ,Body Size ,GENETICS & HEREDITY ,2. Zero hunger ,Genetics ,Genetics & Heredity ,RISK ,0303 health sciences ,Neuronal growth regulator 1 ,Genetics of obesity ,COMMON VARIANTS ,Chromosome Mapping ,11 Medical And Health Sciences ,Body Height/genetics ,Body Size/genetics ,Body Weight/genetics ,European Continental Ancestry Group/genetics ,Genetic Predisposition to Disease/genetics ,Genome-Wide Association Study ,Humans ,Obesity/genetics ,Polymorphism, Single Nucleotide ,FAT MASS ,Body Height/*genetics *Body Mass Index Body Size/genetics Body Weight/*genetics *Chromosome Mapping European Continental Ancestry Group/genetics Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,MELANOCORTIN-4 RECEPTOR GENE ,Life Sciences & Biomedicine ,European Continental Ancestry Group ,EARLY-ONSET ,030209 endocrinology & metabolism ,Locus (genetics) ,Biology ,Article ,White People ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,body mass index ,genome-wide association ,meta-analysis ,Genetic Predisposition to Disease ,Obesity ,GENOME-WIDE ASSOCIATION ,FTO GENE ,030304 developmental biology ,Science & Technology ,genome-wide association gastric-inhibitory polypeptide melanocortin-4 receptor gene glucose-homeostasis common variants adult obesity early-onset fat mass risk metaanalysis ,Body Weight ,06 Biological Sciences ,MAGIC ,Body Height ,GLUCOSE-HOMEOSTASIS ,Procardis Consortium ,Body mass index ,Developmental Biology - Abstract
Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.
- Published
- 2010
26. Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.
- Author
-
Muntner P, Hernandez RK, Kent ST, Browning JE, Gilbertson DT, Hurwitz KE, Jick SS, Lai EC, Lash TL, Monda KL, Rothman KJ, Bradbury BD, and Brookhart MA
- Subjects
- Humans, Bias, Policy
- Abstract
Purpose: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room., Methods: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail. These constructs are intended to allow decisions about protocol deviations, such as changes to design or model specification, to be made without knowledge of how they might affect subsequent analyses. We describe an example for implementing staging with a clean room., Results: Stage 1 may involve selecting a data source, developing and registering a protocol, establishing a clean room, and applying inclusion/exclusion criteria. Stage 2 may involve attempting to achieve covariate balance, often through propensity score models. Stage 3 may involve evaluating the presence of residual confounding using negative control outcomes. After each stage, check points may be implemented when a team of statisticians, epidemiologists and clinicians masked to how their decisions may affect study outcomes, reviews the results. This review team may be tasked with making recommendations for protocol deviations to address study precision or bias. They may recommend proceeding to the next stage, conducting additional analyses to address bias, or terminating the study. Stage 4 may involve conducting the comparative analyses., Conclusions: The staging and clean room constructs are intended to protect the integrity and enhance confidence in the results of analyses of RWD., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
27. Retrospective comparison of traditional and artificial intelligence-based heart failure phenotyping in a US health system to enable real-world evidence.
- Author
-
Garan AR, Monda KL, Dent-Acosta RE, Riskin DJ, and Gluckman TJ
- Subjects
- Humans, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Electronic Health Records, Natural Language Processing, Artificial Intelligence, Heart Failure
- Abstract
Objective: Quantitatively evaluate the quality of data underlying real-world evidence (RWE) in heart failure (HF)., Design: Retrospective comparison of accuracy in identifying patients with HF and phenotypic information was made using traditional (ie, structured query language applied to structured electronic health record (EHR) data) and advanced (ie, artificial intelligence (AI) applied to unstructured EHR data) RWE approaches. The performance of each approach was measured by the harmonic mean of precision and recall (F
1 score) using manual annotation of medical records as a reference standard., Setting: EHR data from a large academic healthcare system in North America between 2015 and 2019, with an expected catchment of approximately 5 00 000 patients., Population: 4288 encounters for 1155 patients aged 18-85 years, with 472 patients identified as having HF., Outcome Measures: HF and associated concepts, such as comorbidities, left ventricular ejection fraction, and selected medications., Results: The average F1 scores across 19 HF-specific concepts were 49.0% and 94.1% for the traditional and advanced approaches, respectively (p<0.001 for all concepts with available data). The absolute difference in F1 score between approaches was 45.1% (98.1% relative increase in F1 score using the advanced approach). The advanced approach achieved superior F1 scores for HF presence, phenotype and associated comorbidities. Some phenotypes, such as HF with preserved ejection fraction, revealed dramatic differences in extraction accuracy based on technology applied, with a 4.9% F1 score when using natural language processing (NLP) alone and a 91.0% F1 score when using NLP plus AI-based inference., Conclusions: A traditional RWE generation approach resulted in low data quality in patients with HF. While an advanced approach demonstrated high accuracy, the results varied dramatically based on extraction techniques. For future studies, advanced approaches and accuracy measurement may be required to ensure data are fit-for-purpose., Competing Interests: Competing interests: KLM and RED-A are employees and stockholders of Amgen Inc. DJR is an employee and stockholder of Verantos, Inc. ARG has received research support from Abbott., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
- Full Text
- View/download PDF
28. Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.
- Author
-
Lee MP, Dimos SF, Raffield LM, Wang Z, Ballou AF, Downie CG, Arehart CH, Correa A, de Vries PS, Du Z, Gignoux CR, Gordon-Larsen P, Guo X, Haessler J, Howard AG, Hu Y, Kassahun H, Kent ST, Lopez JAG, Monda KL, North KE, Peters U, Preuss MH, Rich SS, Rhodes SL, Yao J, Yarosh R, Tsai MY, Rotter JI, Kooperberg CL, Loos RJF, Ballantyne C, Avery CL, and Graff M
- Subjects
- Humans, Lipoprotein(a) genetics, Evidence Gaps, Risk Factors, Coronary Artery Disease diagnosis, Coronary Artery Disease epidemiology, Coronary Artery Disease genetics, Myocardial Ischemia
- Abstract
Introduction: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations., Methods: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations., Results: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R
2 =15% in East Asians) to high (R2 =50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10-6 ), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects., Conclusions: Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
- Full Text
- View/download PDF
29. Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.
- Author
-
Poudel B, Rosenson RS, Kent ST, Bittner V, Gutiérrez OM, Anderson AH, Woodward M, Jackson EA, Monda KL, Bajaj A, Huang L, Kansal M, Rahman M, He J, Muntner P, and Colantonio LD
- Abstract
Rationale & Objective: Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD., Study Design: Observational cohort study., Setting & Participants: We included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and 2008., Exposure: Baseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay., Outcomes: Recurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through 2019., Analytical Approach: We used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs., Results: Among participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs = 0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death., Limitations: Lipoprotein(a) was not available in molar concentration., Conclusions: Lipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure., (© 2023 The Authors.)
- Published
- 2023
- Full Text
- View/download PDF
30. Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults With Cardiovascular Disease.
- Author
-
Colantonio LD, Bittner V, Safford MM, Marcovina S, Brown TM, Jackson EA, Li M, López JAG, Monda KL, Plante TB, Kent ST, Muntner P, and Rosenson RS
- Subjects
- Adult, C-Reactive Protein, Humans, Lipoprotein(a), Risk Factors, Atherosclerosis, Cardiovascular Diseases, Coronary Disease epidemiology, Ischemic Stroke diagnosis, Ischemic Stroke epidemiology, Stroke epidemiology
- Abstract
Background It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD). Methods and Results We conducted a case-cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log-transformed lipoprotein(a) was 1.26 (95% CI, 1.02-1.56) among Black participants and 1.16 (95% CI, 1.02-1.31) among White participants ( P value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log-lipoprotein(a) within subgroups with hs-CRP (high-sensitivity C-reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99-1.73) and 1.23 (95% CI, 0.85-1.80), respectively ( P value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91-1.27) and 1.36 (95% CI, 1.10-1.70), respectively ( P value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants. Conclusions Higher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.
- Published
- 2022
- Full Text
- View/download PDF
31. Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study.
- Author
-
Mefford MT, Chen L, Lewis CE, Muntner P, Sidney S, Launer LJ, Monda KL, Ruzza A, Kassahun H, Rosenson RS, and Carson AP
- Subjects
- Adolescent, Adult, Cohort Studies, Humans, Middle Aged, Prospective Studies, Stroop Test, Young Adult, Cholesterol, LDL blood, Cognition
- Abstract
Objectives: It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults., Methods: Lipids were measured at baseline (1985-1986; age: 18-30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes., Results: There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101-129 mg/dL, 130-159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV., Conclusion: Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.
- Published
- 2021
- Full Text
- View/download PDF
32. Race/ethnic and sex differences in the initiation of non-statin lipid-lowering medication following myocardial infarction.
- Author
-
Colvin CL, Poudel B, Bress AP, Derington CG, King JB, Wen Y, Chen L, Bittner V, Brown TM, Monda KL, Mues KE, Rosenson RS, Jackson EA, Muntner P, and Colantonio LD
- Subjects
- Aged, Aged, 80 and over, Coronary Artery Disease ethnology, Female, Heart Disease Risk Factors, Humans, Male, Retrospective Studies, Anticholesteremic Agents administration & dosage, Coronary Artery Disease etiology, Coronary Artery Disease prevention & control, Ezetimibe administration & dosage, Myocardial Infarction complications, PCSK9 Inhibitors administration & dosage, Racial Groups, Sex Characteristics
- Abstract
Background: Adults with atherosclerotic cardiovascular disease (ASCVD) at very high-risk for recurrent events who have low-density lipoprotein cholesterol ≥ 70 mg/dL despite maximally-tolerated statin therapy are recommended to initiate ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor., Objective: Compare the initiation of ezetimibe and a PCSK9 inhibitor after a myocardial infarction (MI) among very high-risk ASCVD patients by race/ethnicity and sex., Methods: We analyzed data from 374,786 adults ≥ 66 years of age with Medicare fee-for-service coverage who had an MI between July 1, 2015 and December 31, 2018, were not taking ezetimibe or a PCSK9 inhibitor, and had very high-risk ASCVD defined by the 2018 American Heart Association/American College of Cardiology multi-society cholesterol guideline. Pharmacy claims through December 31, 2018 were used to determine ezetimibe and PCSK9 inhibitor initiation., Results: Overall, 6980 (1.9%) beneficiaries initiated ezetimibe, and 1433 (0.4%) initiated a PCSK9 inhibitor. Adjusted hazard ratios (aHR) for ezetimibe initiation among non-Hispanic Black, Hispanic, and Asian versus non-Hispanic White beneficiaries were 0.77 (95% confidence interval [95%CI]: 0.70-0.86), 0.92 (95%CI: 0.76-1.11) and 0.73 (95%CI: 0.59-0.89), respectively. Compared to non-Hispanic White beneficiaries, the aHRs for PCSK9 inhibitor initiation were 0.63 (95%CI: 0.48-0.81) among non-Hispanic Black, 0.70 (95%CI: 0.43-1.13) among Hispanic, and 0.93 (95%CI: 0.62-1.39) among Asian beneficiaries. The aHRs for ezetimibe and PCSK9 inhibitor initiation comparing women to men were 1.11 (95%CI: 1.06-1.17) and 1.13 (95%CI: 1.01-1.25), respectively., Conclusion: There are race/ethnic and sex disparities in the initiation of ezetimibe and a PCSK9 inhibitor following MI among very high-risk ASCVD patients., (Copyright © 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
33. Death, long-term nursing home placement, and impoverishment after recurrent myocardial infarction.
- Author
-
Levitan EB, Poudel B, Huang L, Zhao H, Bittner V, Safford MM, Jackson EA, Monda KL, and Muntner P
- Abstract
Study Objective: To determine whether recurrent myocardial infarction (MI) is associated with increased risk of mortality, long-term nursing home placement, and impoverishment., Design: Retrospective cohort study., Setting: United States Medicare program., Participants: Individuals age > 65 years with recurrent MI hospitalizations ( n = 228,826) between January 1, 2007 and June 30, 2017 and controls with initial but not recurrent MI ( n = 915,304)., Main Outcome Measures: Death, nursing home placement, and impoverishment (Medicaid enrollment or subsidies for low-income and -resource individuals) through December 31, 2017., Results: In the recurrent MI and control cohorts, 47% and 41% of individuals were age > 80 years, respectively, and 56% of both cohorts were women. After 1 year, 48% of the recurrent MI cohort and 16% of the control cohort died, 9% and 7% experienced nursing home placement, and 4% and 2% experienced impoverishment. Multivariable-adjusted hazard ratios (95% confidence intervals) comparing the recurrent MI and control cohorts were 2.04 (2.03-2.06) for death, 0.89 (0.88-0.91) for nursing home placement, and 1.32 (1.28-1.36) for impoverishment., Conclusions: Older US adults with recurrent MI had higher risk of death and impoverishment than controls who had experienced an initial MI. Unadjusted, recurrent MI was associated with higher risk of nursing home placement; however, after adjusting for sociodemographic characteristics and comorbidities, individuals with recurrent MI had slightly lower risk of nursing home placement. Preventing recurrent MI may also reduce the risk of death and impoverishment among older US adults., Competing Interests: EBL reports research funding from Amgen and serving as a consultant for a Novartis funded research project. VB reports research funding from Sanofi, AstraZeneca, DalCor, Esperion, and Bayer, and consulting for Sanofi. MMS reports research funding from Amgen. EAJ reports research funding from Amgen and consulting income from McKesson and UpToDate. KLM reports Amgen employment and stock ownership. PM reports research funding from Amgen. The other authors have no interests to report., (© 2021 The Authors.)
- Published
- 2021
- Full Text
- View/download PDF
34. Factors Associated With PCSK9 Inhibitor Initiation Among US Veterans.
- Author
-
Derington CG, Colantonio LD, Herrick JS, Cook J, King JB, Rosenson RS, Poudel B, Monda KL, Navar AM, Mues KE, Stevens VW, Nelson RE, Vanneman ME, Muntner P, and Bress AP
- Subjects
- Aged, Atherosclerosis blood, Atherosclerosis ethnology, Biomarkers blood, Case-Control Studies, Cholesterol, LDL blood, Cholesterol, LDL drug effects, Female, Follow-Up Studies, Humans, Hypercholesterolemia blood, Hypercholesterolemia ethnology, Male, Retrospective Studies, Time Factors, United States epidemiology, Antibodies, Monoclonal, Humanized therapeutic use, Atherosclerosis drug therapy, Ethnicity, Hypercholesterolemia drug therapy, PCSK9 Inhibitors, Racial Groups, Veterans
- Abstract
Background Few adults at high risk for atherosclerotic cardiovascular disease events use a PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor). Methods and Results Using data from the US Veterans Health Administration, we identified veterans who initiated a PCSK9i between January 2018 and December 2019, matched 1:4 to veterans who did not initiate this medication over this time period (case-cohort study). Two cohorts of veterans were analyzed: (1) atherosclerotic cardiovascular disease, with a most recent low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL; and (2) severe hypercholesterolemia (ie, familial hypercholesterolemia or any prior LDL-C ≥190 mg/dL, with most recent LDL-C ≥100 mg/dL). Conditional logistic regression was used to analyze factors associated with PCSK9i initiation, adjusting for all factors, simultaneously. There were 2394 initiators and 9576 noninitiators in the atherosclerotic cardiovascular disease cohort (median LDL-C, 141 and 96 mg/dL, respectively; P <0.001). Factors associated with a higher likelihood of PCSK9i initiation included age 65 to <75 versus <65 years, highest versus lowest quartile of median area-level income, familial hypercholesterolemia, former statin use, and current ezetimibe use. PCSK9i initiation was lower among veterans of a race/ethnicity other than non-Hispanic White. There were 245 initiators and 980 noninitiators in the severe hypercholesterolemia cohort (median LDL-C, 183 and 151 mg/dL, respectively; P <0.001). Age ≥75 versus <65 years, history of chronic kidney disease, former statin use, and current ezetimibe use were associated with a higher likelihood of PCSK9i initiation. Conclusions Several patient-level factors, including age, sex, and race/ethnicity, were significantly associated with PCSK9i initiation, suggesting an unmet treatment need in several patient groups.
- Published
- 2021
- Full Text
- View/download PDF
35. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.
- Author
-
Graff M, Justice AE, Young KL, Marouli E, Zhang X, Fine RS, Lim E, Buchanan V, Rand K, Feitosa MF, Wojczynski MK, Yanek LR, Shao Y, Rohde R, Adeyemo AA, Aldrich MC, Allison MA, Ambrosone CB, Ambs S, Amos C, Arnett DK, Atwood L, Bandera EV, Bartz T, Becker DM, Berndt SI, Bernstein L, Bielak LF, Blot WJ, Bottinger EP, Bowden DW, Bradfield JP, Brody JA, Broeckel U, Burke G, Cade BE, Cai Q, Caporaso N, Carlson C, Carpten J, Casey G, Chanock SJ, Chen G, Chen M, Chen YI, Chen WM, Chesi A, Chiang CWK, Chu L, Coetzee GA, Conti DV, Cooper RS, Cushman M, Demerath E, Deming SL, Dimitrov L, Ding J, Diver WR, Duan Q, Evans MK, Falusi AG, Faul JD, Fornage M, Fox C, Freedman BI, Garcia M, Gillanders EM, Goodman P, Gottesman O, Grant SFA, Guo X, Hakonarson H, Haritunians T, Harris TB, Harris CC, Henderson BE, Hennis A, Hernandez DG, Hirschhorn JN, McNeill LH, Howard TD, Howard B, Hsing AW, Hsu YH, Hu JJ, Huff CD, Huo D, Ingles SA, Irvin MR, John EM, Johnson KC, Jordan JM, Kabagambe EK, Kang SJ, Kardia SL, Keating BJ, Kittles RA, Klein EA, Kolb S, Kolonel LN, Kooperberg C, Kuller L, Kutlar A, Lange L, Langefeld CD, Le Marchand L, Leonard H, Lettre G, Levin AM, Li Y, Li J, Liu Y, Liu Y, Liu S, Lohman K, Lotay V, Lu Y, Maixner W, Manson JE, McKnight B, Meng Y, Monda KL, Monroe K, Moore JH, Mosley TH, Mudgal P, Murphy AB, Nadukuru R, Nalls MA, Nathanson KL, Nayak U, N'Diaye A, Nemesure B, Neslund-Dudas C, Neuhouser ML, Nyante S, Ochs-Balcom H, Ogundiran TO, Ogunniyi A, Ojengbede O, Okut H, Olopade OI, Olshan A, Padhukasahasram B, Palmer J, Palmer CD, Palmer ND, Papanicolaou G, Patel SR, Pettaway CA, Peyser PA, Press MF, Rao DC, Rasmussen-Torvik LJ, Redline S, Reiner AP, Rhie SK, Rodriguez-Gil JL, Rotimi CN, Rotter JI, Ruiz-Narvaez EA, Rybicki BA, Salako B, Sale MM, Sanderson M, Schadt E, Schreiner PJ, Schurmann C, Schwartz AG, Shriner DA, Signorello LB, Singleton AB, Siscovick DS, Smith JA, Smith S, Speliotes E, Spitz M, Stanford JL, Stevens VL, Stram A, Strom SS, Sucheston L, Sun YV, Tajuddin SM, Taylor H, Taylor K, Tayo BO, Thun MJ, Tucker MA, Vaidya D, Van Den Berg DJ, Vedantam S, Vitolins M, Wang Z, Ware EB, Wassertheil-Smoller S, Weir DR, Wiencke JK, Williams SM, Williams LK, Wilson JG, Witte JS, Wrensch M, Wu X, Yao J, Zakai N, Zanetti K, Zemel BS, Zhao W, Zhao JH, Zheng W, Zhi D, Zhou J, Zhu X, Ziegler RG, Zmuda J, Zonderman AB, Psaty BM, Borecki IB, Cupples LA, Liu CT, Haiman CA, Loos R, Ng MCY, and North KE
- Subjects
- Africa ethnology, Black or African American genetics, Europe ethnology, Female, Humans, Male, Polymorphism, Single Nucleotide genetics, Black People genetics, Body Height genetics, Genome-Wide Association Study
- Abstract
Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations., (Copyright © 2021 American Society of Human Genetics. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
36. Atherosclerotic Risk and Statin Use Among Patients With Peripheral Artery Disease.
- Author
-
Colantonio LD, Hubbard D, Monda KL, Mues KE, Huang L, Dai Y, Jackson EA, Brown TM, Rosenson RS, Woodward M, Muntner P, and Farkouh ME
- Subjects
- Adult, Aged, Aged, 80 and over, Atherosclerosis epidemiology, Atherosclerosis prevention & control, Female, Follow-Up Studies, Global Health, Humans, Incidence, Male, Middle Aged, Peripheral Arterial Disease epidemiology, Retrospective Studies, Risk Factors, Young Adult, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Peripheral Arterial Disease prevention & control, Risk Assessment methods
- Abstract
Background: Peripheral artery disease (PAD) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) events., Objectives: The goal of this study was to compare the risk for ASCVD events and the use of statins among patients with PAD versus those with coronary heart disease (CHD) or cerebrovascular disease., Methods: The authors conducted a retrospective cohort study of adults age ≥19 years with commercial or Medicare health insurance who had a history of PAD, CHD, or cerebrovascular disease on December 31, 2014. Patients were followed for ASCVD events comprising CHD, cerebrovascular disease, and PAD events until December 31, 2017., Results: Among 943,232 patients included in the analysis, the age-standardized ASCVD event rate per 1,000 person-years for those with a history of 1, 2, and 3 conditions including PAD, CHD, and cerebrovascular disease was 40.8 (95% confidence interval [CI]: 40.3 to 41.3), 68.9 (95% CI: 67.9 to 70.0), and 119.5 (95% CI: 117.0 to 122.0), respectively. The ASCVD event rate among patients with PAD only, CHD only, and cerebrovascular disease only was 34.7 (95% CI: 33.2 to 36.2), 42.2 (95% CI: 41.5 to 42.8), and 38.9 (95% CI: 37.6 to 40.1), respectively. Among patients with PAD and CHD, with PAD and cerebrovascular disease, and with CHD and cerebrovascular disease, the ASCVD event rate was 72.8 (95% CI: 71.0 to 74.7), 63.9 (95% CI: 60.6 to 67.4), and 67.9 (95% CI: 66.4 to 69.3), respectively. Statin use was lower in patients with PAD only (33.9%) versus those with cerebrovascular disease only (43.0%) or CHD only (51.7%)., Conclusions: Despite having high risk for ASCVD events, patients with PAD were less likely to be taking a statin versus those with CHD or cerebrovascular disease. ASCVD risk-reduction interventions including statin therapy in patients with PAD are warranted., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
37. Use of Low-Density Lipoprotein-Lowering Therapies Before and After PCSK9 Inhibitor Initiation.
- Author
-
Rymer JA, Mues KE, Monda KL, Bratton EW, Wirtz HS, Okerson T, Overman RA, Brookhart MA, Muntner P, and Wang TY
- Subjects
- Aged, Biomarkers blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Databases, Factual, Down-Regulation, Drug Prescriptions, Drug Therapy, Combination, Dyslipidemias blood, Dyslipidemias diagnosis, Dyslipidemias epidemiology, Female, Humans, Hypolipidemic Agents adverse effects, Male, Middle Aged, Retrospective Studies, Risk Assessment, Risk Factors, Serine Proteinase Inhibitors adverse effects, Time Factors, Treatment Outcome, United States epidemiology, Cardiovascular Diseases prevention & control, Dyslipidemias drug therapy, Hypolipidemic Agents therapeutic use, Lipoproteins, LDL blood, PCSK9 Inhibitors, Serine Proteinase Inhibitors therapeutic use
- Abstract
Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are used to reduce low-density lipoprotein (LDL) cholesterol. PCSK9i use after initiation, as well as persistence with or alterations to other LDL-lowering therapy after PCSK9i initiation, is not well understood. Methods and Results We conducted a retrospective study of alirocumab or evolocumab (PCSK9i) new users from July 2015 to December 2017 in the MarketScan Early View database of US commercial insurance beneficiaries. We determined the prevalence of PCSK9i interruption (≥30-day gap in supply) and LDL-lowering therapy use in the year after PCSK9i initiation. The average age of 6151 patients initiating PCSK9i therapy was 63 years, 44.4% were women, and 76.8% had atherosclerotic cardiovascular disease. Overall, 52.2% (95% CI, 50.8%-53.7%) of patients had an interruption in PCSK9i therapy in the first year after treatment initiation and 62.5% remained on PCSK9i therapy at 1-year postinitiation. Also, 27.7% of patients were taking a statin at the time of PCSK9i initiation, with only 22.4% on statin therapy at 1 year after PCSK9i initiation. Ezetimibe use decreased from 20.9% at the time of PCSK9i initiation to 12.0% a year later. By 1 year after PCSK9i initiation, 44.0% of patients had experienced an interruption in all LDL-lowering therapies, and 26.6% were no longer on any LDL-lowering therapies. Conclusions After PCSK9i initiation, statins were often discontinued, whereas more than half of patients experienced an interruption in PCSK9i therapy. These results suggest that many new PCSK9i users may remain at high risk for cardiovascular events because of interruptions in LDL-lowering therapy.
- Published
- 2020
- Full Text
- View/download PDF
38. Residual risk for coronary heart disease events and mortality despite intensive medical management after myocardial infarction.
- Author
-
Brown TM, Bittner V, Colantonio LD, Deng L, Farkouh ME, Limdi N, Monda KL, Rosenson RS, Serban MC, Somaratne RM, Zhao H, Woodward M, and Muntner P
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Male, Middle Aged, Myocardial Infarction complications, Retrospective Studies, Risk Factors, Coronary Disease complications, Myocardial Infarction therapy
- Abstract
Background: High-intensity statins, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and antiplatelet agents (ie, intensive medical management) reduce coronary heart disease (CHD) risk after myocardial infarction (MI)., Objective: The objective of the study was to determine the risk of CHD events or death despite receiving intensive medical management after MI., Methods: We studied 16,853 United States adults with health insurance in the MarketScan and Medicare databases who underwent percutaneous coronary intervention while hospitalized for MI between January 1, 2014 and June 30, 2015 and received intensive medical management within 30 days after hospital discharge. MI, CHD, and all-cause mortality rates from 30 days after hospital discharge through December 31, 2015 were compared with 67,412 individuals in each of three groups: (1) the general MarketScan and Medicare populations, (2) with diabetes, and (3) with a CHD history., Results: Among beneficiaries intensively medically managed after their MI, recurrent MI, CHD events, and all-cause mortality rates were 47.1, 72.0, and 57.5 per 1000 person-years, respectively. The multivariable-adjusted hazard ratio (95% CI) comparing intensively medically managed beneficiaries after MI to the general population, those with diabetes, and those with a history of CHD were 8.54 (7.52-9.70), 7.40 (6.61-8.28), and 5.45 (4.92-6.05), respectively, for recurrent MI; 7.82 (7.07-8.64), 6.27 (5.74-6.86), and 4.45 (4.10-4.82), respectively, for CHD events; and 1.15 (1.05-1.25), 1.05 (0.97-1.14), and 1.06 (0.97-1.15), respectively, for all-cause mortality., Conclusion: Substantial residual risk for MI and CHD events remains despite intensive medical management after MI., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
39. Trends in statin utilization among adults with severe peripheral artery disease including critical limb ischemia in an integrated healthcare delivery system.
- Author
-
Reynolds K, Mues KE, Harrison TN, Qian L, Chen S, Hsu JY, Philip KJ, Monda KL, Reading SR, and Brar SS
- Subjects
- Adult, Aged, Aged, 80 and over, California epidemiology, Critical Illness, Drug Utilization trends, Dyslipidemias diagnosis, Dyslipidemias epidemiology, Female, Guideline Adherence trends, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Incidence, Ischemia diagnosis, Ischemia epidemiology, Male, Middle Aged, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease epidemiology, Practice Guidelines as Topic, Retrospective Studies, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Delivery of Health Care, Integrated trends, Dyslipidemias drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Ischemia drug therapy, Peripheral Arterial Disease drug therapy, Practice Patterns, Physicians' trends
- Abstract
Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% ( n = 3442) with CLI and 68.9% ( n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% ( n = 4481) who were not on a statin in the year before diagnosis, 13.5% ( n = 607) newly initiated therapy within 1 month (CLI: 10.1% ( n = 150); without CLI: 15.3% ( n = 457)). Following diagnosis, 12.5% ( n = 660) discontinued statin therapy within 1 year (CLI: 15.5% ( n = 202); without CLI: 11.5% ( n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.
- Published
- 2020
- Full Text
- View/download PDF
40. Excess Risk for Atherosclerotic Cardiovascular Outcomes Among US Adults With HIV in the Current Era.
- Author
-
Rosenson RS, Hubbard D, Monda KL, Reading SR, Chen L, Dluzniewski PJ, Burkholder GA, Muntner P, and Colantonio LD
- Subjects
- Adult, Aged, Anti-HIV Agents therapeutic use, Databases, Factual, Female, HIV Infections diagnosis, HIV Infections drug therapy, Heart Disease Risk Factors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Incidence, Insurance, Medigap, Male, Middle Aged, Myocardial Infarction diagnosis, Peripheral Arterial Disease diagnosis, Prognosis, Retrospective Studies, Risk Assessment, Stroke diagnosis, Time Factors, United States epidemiology, Young Adult, HIV Infections epidemiology, Myocardial Infarction epidemiology, Peripheral Arterial Disease epidemiology, Stroke epidemiology
- Abstract
Background In the 2000s, adults with HIV had a higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with those without HIV. There is uncertainty if this excess risk still exists in the United States given changes in antiretroviral therapies and increased statin use. Methods and Results We compared the risk for ASCVD events between US adults aged ≥19 years with and without HIV who had commercial or supplemental Medicare health insurance between January 1, 2011, and December 31, 2016. Beneficiaries with HIV (n=82 426) were frequency matched 1:4 on age, sex, and calendar year to those without HIV (n=329 704). Beneficiaries with and without HIV were followed up through December 31, 2016, for ASCVD events, including myocardial infarction, stroke, and lower extremity artery disease hospitalizations. Most beneficiaries were aged <55 years (79%) and men (84%). Over a median follow-up of 1.6 years (maximum, 6 years), there were 3287 ASCVD events, 2190 myocardial infarctions, 891 strokes, and 322 lower extremity artery disease events. The rate per 1000 person-years among beneficiaries with and without HIV was 5.53 and 3.49 for ASCVD, respectively, 3.58 and 2.34 for myocardial infarction, respectively, 1.49 and 0.94 for stroke, respectively, and 0.65 and 0.31 for lower extremity artery disease hospitalizations, respectively. The multivariable-adjusted hazard ratio (95% CI) for ASCVD, myocardial infarction, stroke, and lower extremity artery disease hospitalizations comparing beneficiaries with versus without HIV was 1.29 (1.18-1.40), 1.26 (1.13-1.39), 1.30 (1.11-1.52), and 1.46 (1.11-1.92), respectively. Conclusions Adults with HIV in the United States continue to have a higher ASCVD risk compared with their counterparts without HIV.
- Published
- 2020
- Full Text
- View/download PDF
41. PCSK9 loss-of-function variants and Lp(a) phenotypes among black US adults.
- Author
-
Mefford MT, Marcovina SM, Bittner V, Cushman M, Brown TM, Farkouh ME, Tsimikas S, Monda KL, López JAG, Muntner P, and Rosenson RS
- Subjects
- Female, Humans, Male, Middle Aged, Phenotype, Proprotein Convertase 9 deficiency, Proprotein Convertase 9 metabolism, United States, Black or African American genetics, Lipoprotein(a) genetics, Loss of Function Mutation genetics, Proprotein Convertase 9 genetics
- Abstract
The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively ( P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats ( P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM ( P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels., (Copyright © 2019 Mefford et al.)
- Published
- 2019
- Full Text
- View/download PDF
42. Real world evidence in cardiovascular medicine: ensuring data validity in electronic health record-based studies.
- Author
-
Hernandez-Boussard T, Monda KL, Crespo BC, and Riskin D
- Subjects
- Data Mining methods, Datasets as Topic, Humans, Machine Learning, Natural Language Processing, Retrospective Studies, Artificial Intelligence, Cardiology, Cardiovascular Diseases diagnosis, Electronic Health Records, Information Storage and Retrieval methods
- Abstract
Objective: With growing availability of digital health data and technology, health-related studies are increasingly augmented or implemented using real world data (RWD). Recent federal initiatives promote the use of RWD to make clinical assertions that influence regulatory decision-making. Our objective was to determine whether traditional real world evidence (RWE) techniques in cardiovascular medicine achieve accuracy sufficient for credible clinical assertions, also known as "regulatory-grade" RWE., Design: Retrospective observational study using electronic health records (EHR), 2010-2016., Methods: A predefined set of clinical concepts was extracted from EHR structured (EHR-S) and unstructured (EHR-U) data using traditional query techniques and artificial intelligence (AI) technologies, respectively. Performance was evaluated against manually annotated cohorts using standard metrics. Accuracy was compared to pre-defined criteria for regulatory-grade. Differences in accuracy were compared using Chi-square test., Results: The dataset included 10 840 clinical notes. Individual concept occurrence ranged from 194 for coronary artery bypass graft to 4502 for diabetes mellitus. In EHR-S, average recall and precision were 51.7% and 98.3%, respectively and 95.5% and 95.3% in EHR-U, respectively. For each clinical concept, EHR-S accuracy was below regulatory-grade, while EHR-U met or exceeded criteria, with the exception of medications., Conclusions: Identifying an appropriate RWE approach is dependent on cohorts studied and accuracy required. In this study, recall varied greatly between EHR-S and EHR-U. Overall, EHR-S did not meet regulatory grade criteria, while EHR-U did. These results suggest that recall should be routinely measured in EHR-based studes intended for regulatory use. Furthermore, advanced data and technologies may be required to achieve regulatory grade results., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association.)
- Published
- 2019
- Full Text
- View/download PDF
43. Lipid-Lowering Prescription Patterns in Patients With Diabetes Mellitus or Cardiovascular Disease.
- Author
-
Chamberlain AM, Cohen SS, Killian JM, Monda KL, Weston SA, and Okerson T
- Subjects
- Adult, Aged, Cardiovascular Diseases complications, Cardiovascular Diseases diagnosis, Cohort Studies, Diabetes Complications complications, Diabetes Complications diagnosis, Female, Humans, Male, Middle Aged, Minnesota, Risk Factors, Cardiovascular Diseases blood, Cholesterol, LDL blood, Diabetes Complications blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Practice Patterns, Physicians'
- Abstract
The purpose of this study is to describe lipid-lowering therapy (LLT) prescriptions and low-density lipoprotein cholesterol (LDL-C) monitoring in patients with diabetes mellitus (DM) with or without concomitant cardiovascular disease (CVD). Olmsted County, Minnesota residents with a first-ever diagnosis of DM or CVD (ischemic stroke/transient ischemic attack, myocardial infarction, unstable angina pectoris, or revascularization procedure) between 2005 and 2012 were classified as having DM only, CVD only, or CVD + DM. All LLT prescriptions and LDL-C measurements were obtained for 2 years after diagnosis. A total of 4,186, 2,368, and 724 patients had DM, CVD, and CVD + DM, respectively. Rates of LDL-C measurement were 1.31, 1.66, and 1.88 per person-year and 14%, 32%, and 42% of LDL-C measurements were <70 mg/dl in those with DM, CVD, and CVD + DM. Within 3 months after diagnosis, 47%, 71%, and 78% of patients with DM, CVD, and CVD + DM were prescribed LLT. Most prescriptions were for moderate-intensity statins. Under one-fifth of patients with CVD and CVD + DM were prescribed high-intensity statins. Predictors of high-intensity statin prescriptions included male sex, having CVD or CVD + DM, increasing LDL-C, and LDL-C measured more recently (2012 to 2014 vs before 2012). In conclusion, a large proportion of patients at high CVD risk are not adequately treated with LLT. Despite often being considered a risk equivalent, patients with DM have substantially lower rates of LLT prescriptions and lesser controlled LDL-C than those with CVD or CVD + DM., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
44. Fibrinogen Columbus II: A novel c.1075G>T mutation in the FGG gene causing hypodysfibrinogenemia and thrombosis in an adolescent male.
- Author
-
Kumar R, Dawson J, Varga E, Canini JT, Monda KL, and Dunn AL
- Subjects
- Adolescent, Binding Sites, Calcium chemistry, Calcium metabolism, Humans, Male, Afibrinogenemia genetics, Afibrinogenemia metabolism, Fibrinogens, Abnormal chemistry, Fibrinogens, Abnormal genetics, Fibrinogens, Abnormal metabolism, Heterozygote, Point Mutation, Venous Thrombosis genetics, Venous Thrombosis metabolism, Venous Thrombosis pathology
- Abstract
Hypodysfibrinogenemia, the least frequently reported congenital fibrinogen disorder is characterized by low circulating levels of a dysfunctional protein, and is associated with phenotypic features of both hypo- and dysfibrinogenemia. Herein, we report an adolescent male with unprovoked venous thromboembolism and hypodysfibrinogenemia. Patient had recurrent, progressive thrombosis despite therapeutic anticoagulation with both low molecular weight heparin and warfarin. He had clinical and radiological improvement after transition to a direct thrombin inhibitor. Sequencing of the FGG gene identified a novel heterozygous mutation, c.1075G>T. Structural visualization of the identified variant was pursued and suggested that the mutation likely destabilizes the Ca
2+ -binding site of fibrinogen resulting in pathogenicity., (© 2019 Wiley Periodicals, Inc.)- Published
- 2019
- Full Text
- View/download PDF
45. Association of Region and Hospital and Patient Characteristics With Use of High-Intensity Statins After Myocardial Infarction Among Medicare Beneficiaries.
- Author
-
Bittner V, Colantonio LD, Dai Y, Woodward M, Mefford MT, Rosenson RS, Muntner P, Monda KL, Kilgore ML, Jaeger BC, and Levitan EB
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Correlation of Data, Female, Humans, Male, Medicare, Patient Discharge, Retrospective Studies, United States, Aftercare statistics & numerical data, Atorvastatin therapeutic use, Drug Utilization statistics & numerical data, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Myocardial Infarction, Rosuvastatin Calcium therapeutic use
- Abstract
Importance: High-intensity statin use after myocardial infarction (MI) varies by patient characteristics, but little is known about differences in use by hospital or region., Objective: To explore the relative strength of associations of region and hospital and patient characteristics with high-intensity statin use after MI., Design, Setting, and Participants: This retrospective cohort analysis used Medicare administrative claims and enrollment data to evaluate fee-for-service Medicare beneficiaries 66 years or older who were hospitalized for MI from January 1, 2011, through June 30, 2015, with a statin prescription claim within 30 days of discharge. Data were analyzed from January 4, 2017, through May 12, 2019., Exposures: Beneficiary characteristics were abstracted from Medicare data. Hospital characteristics were obtained from the 2014 American Hospital Association Survey and Hospital Compare quality metrics. Nine regions were defined according to the US Census., Main Outcomes and Measures: Intensity of the first statin claim after discharge characterized as high (atorvastatin calcium, 40-80 mg, or rosuvastatin calcium, 20-40 mg/d) vs low to moderate (all other statin types and doses). Trends in high-intensity statins were examined from 2011 through 2015. Associations of region and beneficiary and hospital characteristics with high-intensity statin use from January 1, 2014, to June 15, 2015, were examined using Poisson distribution mixed models., Results: Among the 139 643 fee-for-service beneficiaries included (69 968 men [50.1%] and 69 675 women [49.9%]; mean [SD] age, 76.7 [7.5] years), high-intensity statin use overall increased from 23.4% in 2011 to 55.6% in 2015, but treatment gaps persisted across regions. In models considering region and beneficiary and hospital characteristics, region was the strongest correlate of high-intensity statin use, with 66% higher use in New England than in the West South Central region (risk ratio [RR], 1.66; 95% CI, 1.47-1.87). Hospital size of at least 500 beds (RR, 1.15; 95% CI, 1.07-1.23), medical school affiliation (RR, 1.11; 95% CI, 1.05-1.17), male sex (RR, 1.10; 95% CI, 1.07-1.13), and patient receipt of a stent (RR, 1.35; 95% CI, 1.31-1.39) were associated with greater high-intensity statin use. For-profit hospital ownership, patient age older than 75 years, prior coronary disease, and other comorbidities were associated with lower use., Conclusions and Relevance: This study's findings suggest that geographic region is the strongest correlate of high-intensity statin use after MI, leading to large treatment disparities.
- Published
- 2019
- Full Text
- View/download PDF
46. Familial Hypercholesterolemia Among Young Adults With Myocardial Infarction.
- Author
-
Singh A, Gupta A, Collins BL, Qamar A, Monda KL, Biery D, Lopez JAG, de Ferranti SD, Plutzky J, Cannon CP, Januzzi JL Jr, Di Carli MF, Nasir K, Bhatt DL, and Blankstein R
- Subjects
- Adult, Cholesterol, LDL blood, Female, Humans, Hyperlipoproteinemia Type II blood, Hyperlipoproteinemia Type II drug therapy, Male, Prevalence, Registries, Retrospective Studies, Risk Factors, ST Elevation Myocardial Infarction blood, United States epidemiology, Young Adult, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipoproteinemia Type II epidemiology, ST Elevation Myocardial Infarction epidemiology
- Abstract
Background: There are limited data on the prevalence and treatment of familial hypercholesterolemia (FH) among U.S. adults who experience a myocardial infarction (MI) at a young age., Objectives: This study aimed to evaluate the prevalence of clinically defined FH and examine the rates of statin utilization and low-density lipoprotein cholesterol (LDL-C) achieved 1-year post MI., Methods: The YOUNG-MI registry is a retrospective cohort study that includes patients who experience an MI at or below age 50 years between 2000 and 2016 at 2 academic centers. Probable or definite FH was defined by the Dutch Lipid Clinic criteria. Outcomes included the proportion of patients classified as probable or definite FH, use of lipid-lowering therapy, and LDL-C achieved 1-year post MI., Results: The cohort consisted of 1,996 adults with a median age of 45 years; 19% were women, and 54% had ST-segment elevation MI. Probable/definite FH was present in 180 (9%) of whom 42.8% were not on statins prior to their MI. Of the 1,966 patients surviving until hospital discharge, 89.4% of FH patients and 89.9% of non-FH patients were discharged on statin therapy (p = 0.82). Among FH patients, 63.3% were discharged on high-intensity statin compared with 48.4% for non-FH patients (p < 0.001). At 1-year follow-up, the percent reduction in LDL-C among FH patients was -44.4% compared with -34.5% (p = 0.006) in non-FH patients. The proportion of patients with LDL-C ≥70 mg/dl was higher among FH patients (82.2%) compared with non-FH patients (64.5%; p < 0.001)., Conclusions: Clinically defined FH was present in nearly 1 of 10 patients with MI at a young age. Only two-thirds of FH patients were discharged on high-intensity statin therapy, and the vast majority had elevated LDL-C at 1 year. These findings reinforce the need for more aggressive lipid-lowering therapy in young FH and non-FH patients post-MI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
47. Characteristics and Cardiovascular Disease Event Rates among African Americans and Whites Who Meet the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) Trial Inclusion Criteria.
- Author
-
Colantonio LD, Monda KL, Rosenson RS, Brown TM, Mues KE, Howard G, Safford MM, Yedigarova L, Farkouh ME, and Muntner P
- Subjects
- Aged, Aged, 80 and over, Anticholesteremic Agents adverse effects, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases ethnology, Cardiovascular Diseases mortality, Clinical Decision-Making, Clinical Trials as Topic, Databases, Factual, Dyslipidemias blood, Dyslipidemias ethnology, Dyslipidemias mortality, Female, Humans, Male, Middle Aged, Patient Selection, Risk Assessment, Risk Factors, Serine Proteinase Inhibitors adverse effects, Time Factors, Treatment Outcome, United States epidemiology, Black or African American, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases prevention & control, Dyslipidemias drug therapy, Lipids blood, PCSK9 Inhibitors, Serine Proteinase Inhibitors therapeutic use, White People
- Abstract
Purpose: Determine the risk for cardiovascular disease (CVD) events among adults with clinically evident CVD who meet the inclusion criteria for the FOURIER clinical trial on PCSK9 inhibition in a real-world database., Methods: We analyzed data from 2072 African American and 2972 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 45-85 years of age with clinically evident CVD. Study participants meeting the FOURIER inclusion criteria (one major or two minor cardiovascular risk factors, fasting LDL cholesterol ≥ 70 mg/dL or non-HDL cholesterol ≥ 100 mg/dL, triglycerides ≤ 400 mg/dL, and taking statin) were followed for CVD events (myocardial infarction, stroke, coronary revascularization, and CVD death) from baseline in 2003-2007 through 2014., Results: Overall, 771 (37.2%) African Americans and 1200 (40.4%) whites met the FOURIER inclusion criteria. The CVD event rate per 1000 person years was 60.6 (95% CI 53.6-67.6) among African Americans and 63.5 (95% CI 57.7-69.3) among whites. The risk for CVD events among adults meeting the FOURIER inclusion criteria was higher for those with a history of multiple cardiovascular events (hazard ratios among African Americans and whites 1.34 [95% CI 1.05-1.71] and 1.34 [1.10-1.63], respectively), a prior coronary revascularization (1.44 [1.13-1.84] and 1.23 [1.00-1.52], respectively), diabetes (1.38 [1.08-1.76] and 1.41 [1.15-1.72], respectively), reduced glomerular filtration rate (1.63 [1.26-2.11] and 1.29 [1.03-1.62], respectively), and albuminuria (1.77 [1.37-2.27] and 1.33 [1.07-1.65], respectively)., Conclusions: The CVD event rate is high among African Americans and whites meeting the FOURIER inclusion criteria. Characteristics associated with a higher CVD risk may inform the decision to initiate PCSK9 inhibition.
- Published
- 2019
- Full Text
- View/download PDF
48. Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.
- Author
-
Gilbertson DT, Rothman KJ, Chertow GM, Bradbury BD, Brookhart MA, Liu J, Winkelmayer WC, Stürmer T, Monda KL, Herzog CA, Ashfaq A, Collins AJ, and Wetmore JB
- Subjects
- Humans, Kidney Failure, Chronic therapy, Kidney Transplantation, Renal Dialysis, Seasons, Time Factors, United States epidemiology, Influenza, Human complications, Influenza, Human mortality, Kidney Failure, Chronic complications, Kidney Failure, Chronic mortality
- Abstract
Background: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified., Methods: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths., Results: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year., Conclusions: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population., (Copyright © 2019 by the American Society of Nephrology.)
- Published
- 2019
- Full Text
- View/download PDF
49. Trends in Statin Use Among US Adults With Chronic Kidney Disease, 1999-2014.
- Author
-
Mefford MT, Rosenson RS, Deng L, Tanner RM, Bittner V, Safford MM, Coll B, Mues KE, Monda KL, and Muntner P
- Subjects
- Adult, Cardiovascular Diseases etiology, Female, Follow-Up Studies, Glomerular Filtration Rate drug effects, Humans, Male, Middle Aged, Prevalence, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic physiopathology, Retrospective Studies, Risk Factors, United States epidemiology, Young Adult, Cardiovascular Diseases prevention & control, Forecasting, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Nutrition Surveys, Renal Insufficiency, Chronic complications
- Abstract
Background The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recognize cardiovascular disease and diabetes mellitus but not chronic kidney disease ( CKD ) as high-risk conditions warranting statin therapy. Statin use may be lower for adults with CKD compared with adults with conditions that have guideline indications for statin use. Methods and Results We analyzed data from the National Health and Nutrition Examination Surveys from 1999-2002 through 2011-2014 to determine trends in the percentage of US adults ≥20 years of age with and without CKD taking statins. CKD was defined by an estimated glomerular filtration rate <60 mL/min per 1.73m
2 or albumin-to-creatinine ratio ≥30 mg/g. Statin use was identified through a medication inventory. Between 1999-2002 and 2011-2014, the percentage of adults taking statins increased from 17.6% to 35.7% among those with CKD and from 6.8% to 14.7% among those without CKD . After multivariable adjustment, adults with CKD were not more likely to be taking statins compared with those without CKD (prevalence ratio, 1.01; 95% CI] 0.96-1.08). Among adults without a history of cardiovascular disease, those with CKD but not diabetes mellitus were less likely to be taking statins compared with those with diabetes mellitus but not CKD (prevalence ratio, 0.54; 95% CI , 0.44-0.66). Among adults with a history of cardiovascular disease, there was no difference in statin use between those with CKD but not diabetes mellitus versus those with diabetes mellitus but not CKD (prevalence ratio, 0.95; 95% CI , 0.79-1.15). Conclusions CKD does not appear to be a major stimulus for statin use among US adults.- Published
- 2019
- Full Text
- View/download PDF
50. Adherence to Statin Therapy Among US Adults Between 2007 and 2014.
- Author
-
Colantonio LD, Rosenson RS, Deng L, Monda KL, Dai Y, Farkouh ME, Safford MM, Philip K, Mues KE, and Muntner P
- Subjects
- Adult, Age Distribution, Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases epidemiology, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Prognosis, Retrospective Studies, United States epidemiology, Young Adult, Cardiovascular Diseases prevention & control, Medication Adherence statistics & numerical data, Secondary Prevention methods
- Abstract
Background Prior studies suggest that persistence with and adherence to statin therapy is low. Interventions to improve statin persistence and adherence have been developed over the past decade. Methods and Results This was a retrospective cohort study of adults aged ≥21 y with commercial or government health insurance in the MarketScan (Truven Health Analytics) and Medicare databases who initiated statins in 2007-2014 and (1) started treatment after a myocardial infarction (n=201 573), (2) had diabetes mellitus but without coronary heart disease (CHD; n=610 049), or (3) did not have CHD or diabetes mellitus (n=2 244 868). Persistence with (ie, not discontinuing treatment) and high adherence to statin therapy were assessed using pharmacy fills in the year following treatment initiation. In 2007 and 2014, the proportions of patients persistent with statin therapy were 78.1% and 79.1%, respectively, among those initiating treatment following myocardial infarction; 66.5% and 67.3%, respectively, for those with diabetes mellitus but without CHD; and 64.3% and 63.9%, respectively, for those without CHD or diabetes mellitus. Between 2007 and 2014, high adherence to statin therapy increased from 57.9% to 63.8% among patients initiating treatment following myocardial infarction and from 34.9% to 37.6% among those with diabetes mellitus but without CHD (each P
trend <0.001). Among patients without CHD or diabetes mellitus, high adherence did not improve between 2007 (35.7%) and 2014 (36.8%; Ptrend =0.14). In 2014, statin adherence was lower among younger, black, and Hispanic patients versus white patients and those initiating a high-intensity statin dosage. Statin adherence was higher among men and patients with cardiologist care following treatment initiation. Conclusions Persistence with and adherence to statin therapy remain low, particularly among those without CHD.- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.