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1. Trends in treatments of thyroid disease following iodine fortification in Denmark: a nationwide register-based study

Author: Møllehave LT, Linneberg A, Skaaby T, Knudsen N, Jørgensen T, and Thuesen BH
Subjects: iodine, pharmacoepidemiology, thyroid diseases, Infectious and parasitic diseases, RC109-216
Abstract: Line Tang Møllehave,1 Allan Linneberg,1–3 Tea Skaaby,1 Nils Knudsen,4 Torben Jørgensen,1,5,6 Betina Heinsbæk Thuesen1 1Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark; 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 3Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark; 4Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Copenhagen, Denmark; 5Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 6Faculty of Medicine, Aalborg University, Aalborg, Denmark Background: Long-term iodine exposure may influence the frequency of thyroid disease treatments through fluctuations in thyroid diseases. Yet, the long-term fluctuations in thyroid disease treatments upon iodine fortification (IF) are not fully known. We aimed to examine the development in thyroid disease treatments in Denmark before and following the implementation of IF in 2000. Methods: Nationwide data on antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment were obtained from Danish registries. Negative binominal regression was applied to analyze annual changes in treatment rates adjusted for region of residence, sex, and age. Results: Incidence of antithyroid medication transiently increased but fell and reached steady state from 2010 at an incidence rate ratio (RR) of 0.72 (95% confidence interval [CI] 0.67–0.77) compared to year 2000. Thyroid hormone therapy increased and reached steady state in 2010 at an incidence RR of 1.75 (95% CI 1.62–1.89) compared to year 2000. Thyroid surgery was constant except for higher rates in 2014–2015, and radioiodine treatment fluctuated with no apparent pattern. Conclusion: Ten years after IF, a steady state was observed for incident antithyroid medication below the level at IF, and thyroid hormone therapy above the level at IF. Only small changes were observed in thyroid surgery and radioiodine treatment. In the same period, changes in diagnostic and treatment practices and lifestyle factors are likely to have occurred and should be considered when evaluating the effects of IF on treatment of thyroid diseases. Keywords: iodine, pharmacoepidemiology, thyroid diseases
Published: 2018

2. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author: Zhou, B, Carrillo-Larco, RM, Danaei, G, Riley, LM, Paciorek, CJ, Stevens, GA, Gregg, EW, Bennett, JE, Solomon, B, Singleton, RK, Sophiea, MK, Iurilli, MLC, Lhoste, VPF, Cowan, MJ, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, AP, Khang, Y-H, Kim, HC, Laxmaiah, A, Lin, H-H, Margozzini Maira, P, Miranda, JJ, Neuhauser, H, Sundström, J, Varghese, C, Widyahening, IS, Zdrojewski, T, Abarca-Gómez, L, Abdeen, ZA, Abdul Rahim, HF, Abu-Rmeileh, NM, Acosta-Cazares, B, Adams, RJ, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, IA, Aghazadeh-Attari, J, Aguilar-Salinas, CA, Agyemang, C, Ahmad, NA, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, SH, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, AlBuhairan, F, AlDhukair, S, Ali, MM, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, DN, Amougou, N, Amouyel, P, Andersen, LB, Anderssen, SA, Anjana, RM, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araújo, J, Ariansen, I, Aris, T, Arku, RE, Arlappa, N, Aryal, KK, Aspelund, T, Assah, FK, Assunção, MCF, Auvinen, J, Avdićová, M, Azevedo, A, Azimi-Nezhad, M, Azizi, F, Azmin, M, Babu, BV, Bahijri, S, Balakrishna, N, Bamoshmoosh, M, Banach, M, Banadinović, M, Bandosz, P, Banegas, JR, Baran, J, Barbagallo, CM, Barceló, A, Barkat, A, Barreto, M, Barros, AJD, Barros, MVG, Bartosiewicz, A, Basit, A, Bastos, JLD, Bata, I, Batieha, AM, Batyrbek, A, Baur, LA, Beaglehole, R, Belavendra, A, Ben Romdhane, H, Benet, M, Benson, LS, Berkinbayev, S, Bernabe-Ortiz, A, Bernotiene, G, Bettiol, H, Bezerra, J, Bhagyalaxmi, A, Bhargava, SK, Bia, D, Biasch, K, Bika Lele, EC, Bikbov, MM, Bista, B, Bjerregaard, P, Bjertness, E, Bjertness, MB, Björkelund, C, Bloch, KV, Blokstra, A, Bo, S, Bobak, M, Boeing, H, Boggia, JG, Boissonnet, CP, Bojesen, SE, Bongard, V, Bonilla-Vargas, A, Bopp, M, Borghs, H, Bovet, P, Boyer, CB, Braeckman, L, Brajkovich, I, Branca, F, Breckenkamp, J, Brenner, H, Brewster, LM, Briceño, Y, Brito, M, Bruno, G, Bueno-de-Mesquita, HB, Bueno, G, Bugge, A, Burns, C, Bursztyn, M, Cabrera de León, A, Cacciottolo, J, Cameron, C, Can, G, Cândido, APC, Capanzana, MV, Čapková, N, Capuano, E, Capuano, V, Cardoso, VC, Carlsson, AC, Carvalho, J, Casanueva, FF, Censi, L, Cervantes-Loaiza, M, Chadjigeorgiou, CA, Chamukuttan, S, Chan, AW, Chan, Q, Chaturvedi, HK, Chaturvedi, N, Chee, ML, Chen, C-J, Chen, F, Chen, H, Chen, S, Chen, Z, Cheng, C-Y, Cheraghian, B, Cherkaoui Dekkaki, I, Chetrit, A, Chien, K-L, Chiolero, A, Chiou, S-T, Chirita-Emandi, A, Chirlaque, M-D, Cho, B, Christensen, K, Christofaro, DG, Chudek, J, Cinteza, E, Claessens, F, Clarke, J, Clays, E, Cohen, E, Concin, H, Cooper, C, Coppinger, TC, Costanzo, S, Cottel, D, Cowell, C, Craig, CL, Crampin, AC, Crujeiras, AB, Cruz, JJ, Csilla, S, Cui, L, Cureau, FV, Cuschieri, S, D'Arrigo, G, d'Orsi, E, Dallongeville, J, Dankner, R, Dantoft, TM, Dauchet, L, Davletov, K, De Backer, G, De Bacquer, D, De Curtis, A, de Gaetano, G, De Henauw, S, de Oliveira, PD, De Ridder, D, De Smedt, D, Deepa, M, Deev, AD, DeGennaro, VJ, Delisle, H, Demarest, S, Dennison, E, Deschamps, V, Dhimal, M, Di Castelnuovo, AF, Dias-da-Costa, JS, Diaz, A, Dickerson, TT, Dika, Z, Djalalinia, S, Do, HTP, Dobson, AJ, Donfrancesco, C, Donoso, SP, Döring, A, Dorobantu, M, Dörr, M, Doua, K, Dragano, N, Drygas, W, Duante, CA, Duboz, P, Duda, RB, Dulskiene, V, Dushpanova, A, Džakula, A, Dzerve, V, Dziankowska-Zaborszczyk, E, Eddie, R, Eftekhar, E, Eggertsen, R, Eghtesad, S, Eiben, G, Ekelund, U, El-Khateeb, M, El Ati, J, Eldemire-Shearer, D, Eliasen, M, Elosua, R, Erasmus, RT, Erbel, R, Erem, C, Eriksen, L, Eriksson, JG, Escobedo-de la Peña, J, Eslami, S, Esmaeili, A, Evans, A, Faeh, D, Fakhretdinova, AA, Fall, CH, Faramarzi, E, Farjam, M, Fattahi, MR, Fawwad, A, Felix-Redondo, FJ, Felix, SB, Ferguson, TS, Fernandes, RA, Fernández-Bergés, D, Ferrante, D, Ferrao, T, Ferrari, M, Ferrario, MM, Ferreccio, C, Ferreira, HS, Ferrer, E, Ferrieres, J, Figueiró, TH, Fink, G, Fischer, K, Foo, LH, Forsner, M, Fouad, HM, Francis, DK, Franco, MDC, Frikke-Schmidt, R, Frontera, G, Fuchs, FD, Fuchs, SC, Fujita, Y, Fumihiko, M, Furdela, V, Furer, A, Furusawa, T, Gaciong, Z, Galbarczyk, A, Galenkamp, H, Galvano, F, Gao, J, Gao, P, Garcia-de-la-Hera, M, Garcia, P, Gareta, D, Garnett, SP, Gaspoz, J-M, Gasull, M, Gazzinelli, A, Gehring, U, Geleijnse, JM, George, R, Ghanbari, A, Ghasemi, E, Gheorghe-Fronea, O-F, Ghimire, A, Gialluisi, A, Giampaoli, S, Gieger, C, Gill, TK, Giovannelli, J, Gironella, G, Giwercman, A, Gkiouras, K, Goldberg, M, Goldsmith, RA, Gomez, LF, Gomula, A, Gonçalves, H, Gonçalves, M, Gonçalves Cordeiro da Silva, B, Gonzalez-Chica, DA, Gonzalez-Gross, M, González-Rivas, JP, González-Villalpando, C, González-Villalpando, M-E, Gonzalez, AR, Gorbea, MB, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Grajda, A, Grammatikopoulou, MG, Gregor, RD, Grodzicki, T, Grosso, G, Gruden, G, Gu, D, Guan, OP, Gudmundsson, EF, Gudnason, V, Guerrero, R, Guessous, I, Guimaraes, AL, Gulliford, MC, Gunnlaugsdottir, J, Gunter, MJ, Gupta, PC, Gupta, R, Gureje, O, Gurzkowska, B, Gutierrez, L, Gutzwiller, F, Ha, S, Hadaegh, F, Haghshenas, R, Hakimi, H, Halkjær, J, Hambleton, IR, Hamzeh, B, Hange, D, Hanif, AAM, Hantunen, S, Hao, J, Hardman, CM, Hari Kumar, R, Hashemi-Shahri, SM, Hata, J, Haugsgjerd, T, Hayes, AJ, He, Y, Heier, M, Hendriks, ME, Henrique, RDS, Henriques, A, Hernandez Cadena, L, Herqutanto, Herrala, S, Heshmat, R, Hill, AG, Ho, SY, Ho, SC, Hobbs, M, Holdsworth, M, Homayounfar, R, Horasan Dinc, G, Horimoto, ARVR, Hormiga, CM, Horta, BL, Houti, L, Howitt, C, Htay, TT, Htet, AS, Htike, MMT, Hu, Y, Huerta, JM, Huhtaniemi, IT, Huiart, L, Huisman, M, Husseini, AS, Huybrechts, I, Hwalla, N, Iacoviello, L, Iannone, AG, Ibrahim, MM, Ibrahim Wong, N, Ikram, MA, Iotova, V, Irazola, VE, Ishida, T, Isiguzo, GC, Islam, M, Islam, SMS, Iwasaki, M, Jackson, RT, Jacobs, JM, Jaddou, HY, Jafar, T, James, K, Jamrozik, K, Janszky, I, Janus, E, Jarvelin, M-R, Jasienska, G, Jelaković, A, Jelaković, B, Jennings, G, Jha, AK, Jiang, CQ, Jimenez, RO, Jöckel, K-H, Joffres, M, Johansson, M, Jokelainen, JJ, Jonas, JB, Jørgensen, T, Joshi, P, Joukar, F, Jóżwiak, J, Juolevi, A, Jurak, G, Jureša, V, Kaaks, R, Kafatos, A, Kajantie, EO, Kalmatayeva, Z, Kalpourtzi, N, Kalter-Leibovici, O, Kampmann, FB, Kannan, S, Karaglani, E, Kårhus, LL, Karki, KB, Katibeh, M, Katz, J, Kauhanen, J, Kaur, P, Kavousi, M, Kazakbaeva, GM, Keil, U, Keinan Boker, L, Keinänen-Kiukaanniemi, S, Kelishadi, R, Kemper, HCG, Keramati, M, Kerimkulova, A, Kersting, M, Key, T, Khader, YS, Khalili, D, Khaw, K-T, Kheiri, B, Kheradmand, M, Khosravi, A, Kiechl-Kohlendorfer, U, Kiechl, S, Killewo, J, Kim, DW, Kim, J, Klakk, H, Klimek, M, Klumbiene, J, Knoflach, M, Kolle, E, Kolsteren, P, Kontto, JP, Korpelainen, R, Korrovits, P, Kos, J, Koskinen, S, Kouda, K, Kowlessur, S, Koziel, S, Kratenova, J, Kriaucioniene, V, Kristensen, PL, Krokstad, S, Kromhout, D, Kruger, HS, Kubinova, R, Kuciene, R, Kujala, UM, Kulaga, Z, Kumar, RK, Kurjata, P, Kusuma, YS, Kutsenko, V, Kuulasmaa, K, Kyobutungi, C, Laatikainen, T, Lachat, C, Laid, Y, Lam, TH, Landrove, O, Lanska, V, Lappas, G, Larijani, B, Latt, TS, Le Coroller, G, Le Nguyen Bao, K, Le, TD, Lee, J, Lehmann, N, Lehtimäki, T, Lemogoum, D, Levitt, NS, Li, Y, Lilly, CL, Lim, W-Y, Lima-Costa, MF, Lin, X, Lin, Y-T, Lind, L, Lingam, V, Linneberg, A, Lissner, L, Litwin, M, Lo, W-C, Loit, H-M, Lopez-Garcia, E, Lopez, T, Lotufo, PA, Lozano, JE, Lukačević Lovrenčić, I, Lukrafka, JL, Luksiene, D, Lundqvist, A, Lundqvist, R, Lunet, N, Lustigová, M, Luszczki, E, Ma, G, Ma, J, Machado-Coelho, GLL, Machado-Rodrigues, AM, Macia, E, Macieira, LM, Madar, AA, Maggi, S, Magliano, DJ, Magriplis, E, Mahasampath, G, Maire, B, Majer, M, Makdisse, M, Malekzadeh, F, Malekzadeh, R, Malhotra, R, Mallikharjuna Rao, K, Malyutina, SK, Maniego, LV, Manios, Y, Mann, JI, Mansour-Ghanaei, F, Manzato, E, Marcil, A, Mårild, SB, Marinović Glavić, M, Marques-Vidal, P, Marques, LP, Marrugat, J, Martorell, R, Mascarenhas, LP, Matasin, M, Mathiesen, EB, Mathur, P, Matijasevich, A, Matlosz, P, Matsha, TE, Mavrogianni, C, Mbanya, JCN, Mc Donald Posso, AJ, McFarlane, SR, McGarvey, ST, McLachlan, S, McLean, RM, McLean, SB, McNulty, BA, Mediene Benchekor, S, Medzioniene, J, Mehdipour, P, Mehlig, K, Mehrparvar, AH, Meirhaeghe, A, Meisinger, C, Mendoza Montano, C, Menezes, AMB, Menon, GR, Mereke, A, Meshram, II, Metspalu, A, Meyer, HE, Mi, J, Michels, N, Mikkel, K, Milkowska, K, Miller, JC, Minderico, CS, Mini, GK, Mirjalili, MR, Mirrakhimov, E, Mišigoj-Duraković, M, Modesti, PA, Moghaddam, SS, Mohajer, B, Mohamed, MK, Mohamed, SF, Mohammad, K, Mohammadi, MR, Mohammadi, Z, Mohammadifard, N, Mohammadpourhodki, R, Mohan, V, Mohanna, S, Mohd Yusoff, MF, Mohebbi, I, Mohebi, F, Moitry, M, Møllehave, LT, Molnár, D, Momenan, A, Mondo, CK, Monterrubio-Flores, E, Monyeki, KDK, Moon, JS, Moosazadeh, M, Moreira, LB, Morejon, A, Moreno, LA, Morgan, K, Moschonis, G, Mossakowska, M, Mostafa, A, Mostafavi, S-A, Mota, J, Motlagh, ME, Motta, J, Moura-dos-Santos, MA, Mridha, MK, Msyamboza, KP, Mu, TT, Muhihi, AJ, Muiesan, ML, Müller-Nurasyid, M, Murphy, N, Mursu, J, Musa, KI, Musić Milanović, S, Musil, V, Mustafa, N, Nabipour, I, Naderimagham, S, Nagel, G, Naidu, BM, Najafi, F, Nakamura, H, Námešná, J, Nang, EEK, Nangia, VB, Narake, S, Ndiaye, NC, Neal, WA, Nejatizadeh, A, Nenko, I, Neovius, M, Nguyen, CT, Nguyen, ND, Nguyen, QV, Nguyen, QN, Nieto-Martínez, RE, Niiranen, TJ, Nikitin, YP, Ninomiya, T, Nishtar, S, Njelekela, MA, Noale, M, Noboa, OA, Noorbala, AA, Norat, T, Nordendahl, M, Nordestgaard, BG, Noto, D, Nowak-Szczepanska, N, Nsour, MA, Nunes, B, O'Neill, TW, O'Reilly, D, Ochimana, C, Oda, E, Odili, AN, Oh, K, Ohara, K, Ohtsuka, R, Olié, V, Olinto, MTA, Oliveira, IO, Omar, MA, Onat, A, Ong, SK, Ono, LM, Ordunez, P, Ornelas, R, Ortiz, PJ, Osmond, C, Ostojic, SM, Ostovar, A, Otero, JA, Overvad, K, Owusu-Dabo, E, Paccaud, FM, Padez, C, Pahomova, E, Paiva, KMD, Pająk, A, Palli, D, Palmieri, L, Pan, W-H, Panda-Jonas, S, Panza, F, Paoli, M, Papandreou, D, Park, S-W, Park, S, Parnell, WR, Parsaeian, M, Pasquet, P, Patel, ND, Pavlyshyn, H, Pećin, I, Pednekar, MS, Pedro, JM, Peer, N, Peixoto, SV, Peltonen, M, Pereira, AC, Peres, KGDA, Peres, MA, Peters, A, Petkeviciene, J, Peykari, N, Pham, ST, Pichardo, RN, Pigeot, I, Pikhart, H, Pilav, A, Pilotto, L, Pitakaka, F, Piwonska, A, Pizarro, AN, Plans-Rubió, P, Polašek, O, Porta, M, Poudyal, A, Pourfarzi, F, Pourshams, A, Poustchi, H, Pradeepa, R, Price, AJ, Price, JF, Providencia, R, Puhakka, SE, Puiu, M, Punab, M, Qasrawi, RF, Qorbani, M, Queiroz, D, Quoc Bao, T, Radić, I, Radisauskas, R, Rahimikazerooni, S, Rahman, M, Raitakari, O, Raj, M, Rakhimova, EM, Ra, Zhou, B, Carrillo-Larco, RM, Danaei, G, Riley, LM, Paciorek, CJ, Stevens, GA, Gregg, EW, Bennett, JE, Solomon, B, Singleton, RK, Sophiea, MK, Iurilli, MLC, Lhoste, VPF, Cowan, MJ, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, AP, Khang, Y-H, Kim, HC, Laxmaiah, A, Lin, H-H, Margozzini Maira, P, Miranda, JJ, Neuhauser, H, Sundström, J, Varghese, C, Widyahening, IS, Zdrojewski, T, Abarca-Gómez, L, Abdeen, ZA, Abdul Rahim, HF, Abu-Rmeileh, NM, Acosta-Cazares, B, Adams, RJ, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, IA, Aghazadeh-Attari, J, Aguilar-Salinas, CA, Agyemang, C, Ahmad, NA, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, SH, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, AlBuhairan, F, AlDhukair, S, Ali, MM, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, DN, Amougou, N, Amouyel, P, Andersen, LB, Anderssen, SA, Anjana, RM, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araújo, J, Ariansen, I, Aris, T, Arku, RE, Arlappa, N, Aryal, KK, Aspelund, T, Assah, FK, Assunção, MCF, Auvinen, J, Avdićová, M, Azevedo, A, Azimi-Nezhad, M, Azizi, F, Azmin, M, Babu, BV, Bahijri, S, Balakrishna, N, Bamoshmoosh, M, Banach, M, Banadinović, M, Bandosz, P, Banegas, JR, Baran, J, Barbagallo, CM, Barceló, A, Barkat, A, Barreto, M, Barros, AJD, Barros, MVG, Bartosiewicz, A, Basit, A, Bastos, JLD, Bata, I, Batieha, AM, Batyrbek, A, Baur, LA, Beaglehole, R, Belavendra, A, Ben Romdhane, H, Benet, M, Benson, LS, Berkinbayev, S, Bernabe-Ortiz, A, Bernotiene, G, Bettiol, H, Bezerra, J, Bhagyalaxmi, A, Bhargava, SK, Bia, D, Biasch, K, Bika Lele, EC, Bikbov, MM, Bista, B, Bjerregaard, P, Bjertness, E, Bjertness, MB, Björkelund, C, Bloch, KV, Blokstra, A, Bo, S, Bobak, M, Boeing, H, Boggia, JG, Boissonnet, CP, Bojesen, SE, Bongard, V, Bonilla-Vargas, A, Bopp, M, Borghs, H, Bovet, P, Boyer, CB, Braeckman, L, Brajkovich, I, Branca, F, Breckenkamp, J, Brenner, H, Brewster, LM, Briceño, Y, Brito, M, Bruno, G, Bueno-de-Mesquita, HB, Bueno, G, Bugge, A, Burns, C, Bursztyn, M, Cabrera de León, A, Cacciottolo, J, Cameron, C, Can, G, Cândido, APC, Capanzana, MV, Čapková, N, Capuano, E, Capuano, V, Cardoso, VC, Carlsson, AC, Carvalho, J, Casanueva, FF, Censi, L, Cervantes-Loaiza, M, Chadjigeorgiou, CA, Chamukuttan, S, Chan, AW, Chan, Q, Chaturvedi, HK, Chaturvedi, N, Chee, ML, Chen, C-J, Chen, F, Chen, H, Chen, S, Chen, Z, Cheng, C-Y, Cheraghian, B, Cherkaoui Dekkaki, I, Chetrit, A, Chien, K-L, Chiolero, A, Chiou, S-T, Chirita-Emandi, A, Chirlaque, M-D, Cho, B, Christensen, K, Christofaro, DG, Chudek, J, Cinteza, E, Claessens, F, Clarke, J, Clays, E, Cohen, E, Concin, H, Cooper, C, Coppinger, TC, Costanzo, S, Cottel, D, Cowell, C, Craig, CL, Crampin, AC, Crujeiras, AB, Cruz, JJ, Csilla, S, Cui, L, Cureau, FV, Cuschieri, S, D'Arrigo, G, d'Orsi, E, Dallongeville, J, Dankner, R, Dantoft, TM, Dauchet, L, Davletov, K, De Backer, G, De Bacquer, D, De Curtis, A, de Gaetano, G, De Henauw, S, de Oliveira, PD, De Ridder, D, De Smedt, D, Deepa, M, Deev, AD, DeGennaro, VJ, Delisle, H, Demarest, S, Dennison, E, Deschamps, V, Dhimal, M, Di Castelnuovo, AF, Dias-da-Costa, JS, Diaz, A, Dickerson, TT, Dika, Z, Djalalinia, S, Do, HTP, Dobson, AJ, Donfrancesco, C, Donoso, SP, Döring, A, Dorobantu, M, Dörr, M, Doua, K, Dragano, N, Drygas, W, Duante, CA, Duboz, P, Duda, RB, Dulskiene, V, Dushpanova, A, Džakula, A, Dzerve, V, Dziankowska-Zaborszczyk, E, Eddie, R, Eftekhar, E, Eggertsen, R, Eghtesad, S, Eiben, G, Ekelund, U, El-Khateeb, M, El Ati, J, Eldemire-Shearer, D, Eliasen, M, Elosua, R, Erasmus, RT, Erbel, R, Erem, C, Eriksen, L, Eriksson, JG, Escobedo-de la Peña, J, Eslami, S, Esmaeili, A, Evans, A, Faeh, D, Fakhretdinova, AA, Fall, CH, Faramarzi, E, Farjam, M, Fattahi, MR, Fawwad, A, Felix-Redondo, FJ, Felix, SB, Ferguson, TS, Fernandes, RA, Fernández-Bergés, D, Ferrante, D, Ferrao, T, Ferrari, M, Ferrario, MM, Ferreccio, C, Ferreira, HS, Ferrer, E, Ferrieres, J, Figueiró, TH, Fink, G, Fischer, K, Foo, LH, Forsner, M, Fouad, HM, Francis, DK, Franco, MDC, Frikke-Schmidt, R, Frontera, G, Fuchs, FD, Fuchs, SC, 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Published: 2021

3. Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Author: Rodriguez-Martinez, Andrea, Zhou, Bin, Sophiea, Marisa K, Bentham, James, Paciorek, Christopher J, Iurilli, Maria LC, Carrillo-Larco, Rodrigo M, Bennett, James E, Di Cesare, Mariachiara, Taddei, Cristina, Bixby, Honor, Stevens, Gretchen A, Riley, Leanne M, Cowan, Melanie J, Savin, Stefan, Danaei, Goodarz, Chirita-Emandi, Adela, Kengne, Andre P, Khang, Young-Ho, Laxmaiah, Avula, Malekzadeh, Reza, Miranda, J Jaime, Moon, Jin Soo, Popovic, Stevo R, Sorensen, Thorkild IA, Soric, Maroje, Starc, Gregor, Zainuddin, Ahmad A, Gregg, Edward W, Bhutta, Zulfiqar A, Black, Robert, Ezzati, Majid, Abarca-Gomez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Othman, Amani Rashed, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiri, Parisa, Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A, Angquist, Lars, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assuncao, Maria Cecilia F, Aung, May Soe, Auvinen, Juha, Avdicova, Maria, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Jorgensen, Maja Baeksgaard, Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, Jose R, Baran, Joanna, Barbagallo, Carlo M, Barcelo, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro Virgilio Gomes, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Ben Romdhane, Habiba, Benedics, Judith, Benet, Mikhail, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Lele, Elysee Claude Bika, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Bjorkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boeing, Heiner, Boggia, Jose G, Bogova, Elena, Boissonnet, Carlos P, Bojesen, Stig E, Bonaccio, Marialaura, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Borghs, 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Susanne R, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, DeGennaro, Vincent, Dehghan, Abbas, Delisle, Helene, Delpeuch, Francis, Demarest, Stefaan, Dennison, Elaine, Deren, Katarzyna, Deschamps, Valerie, Dhana, Klodian, Dhimal, Meghnath, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soares, Diaz-Sanchez, Maria Elena, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Djordjic, Visnja, Do, Ha TP, Dobson, Annette J, Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P, Doring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Doua, Kouamelan, Drygas, Wojciech, Duan, Jia Li, Duante, Charmaine A, Duboz, Priscilla, Duda, Rosemary B, Duleva, Vesselka, Dulskiene, Virginija, Dumith, Samuel C, Dushpanova, Anar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Egbagbe, Eruke E, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elliott, Paul, 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Subjects: Male, body-mass index, ADULTHOOD, Adolescents, pituuskasvu, Pediatrics, Body Mass Index, 0302 clinical medicine, Child Development, nuoret, Public health surveillance, Medicine, Health Status Indicators, 10. No inequality, Child, 11 Medical and Health Sciences, Body mass index, ComputingMilieux_MISCELLANEOUS, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, General Medicine, Body mass indexes, kansainvälinen vertailu, 3. Good health, Geography, Health, 030220 oncology & carcinogenesis, Child, Preschool, Medical and Health sciences, purl.org/becyt/ford/3 [https], medicine.medical_specialty, School-aged adolescents, Socio-culturale, lapset (ikäryhmät), Nursing, territories, ravinto, purl.org/becyt/ford/3.3 [https], 03 medical and health sciences, School Children, SDG 3 - Good Health and Well-being, SYSTEMATIC ANALYSIS, Humans, school-aged children and adolescents, Montenegro, education, Science & Technology, Omvårdnad, Health sciences, Medical and Health sciences, Ciências médicas e da saúde, Bayes Theorem, Anthropometry, Adolescent Development, medicine.disease, TRENDS, Height and Body-mass Index, Faculdade de Ciências Sociais, UNDERNUTRITION, Height index trajectories, Height, body mass index, children , epidemiology, risk factors, growth, Stature, Demography, Settore MED/09 - Medicina Interna, Internationality, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Body-mass index trajectories, Epidemiology, Medicine and Health Sciences, risk factors, countries, EPIDEMIOLOGY, height, children, adolescents, BMI, 030212 general & internal medicine, painoindeksi, Child development, 2. Zero hunger, Medicine(all), School age child, obestity children cardiovascular, Population Health, 1. No poverty, Pediatrik, Public Health, Global Health, Social Medicine and Epidemiology, 3142 Public health care science, environmental and occupational health, Pooled analysis, NUTRITION, Female, medicine.symptom, pooled analysis, Life Sciences & Biomedicine, terveys, height, BMI, nutrition, health, children, adolescents, Adolescent, growth, Population, body-mass, Population based, Body-mass index, Young Adult, Medicine, General & Internal, Meta-Analysis as Topic, General & Internal Medicine, parasitic diseases, Weight gain, School-aged childrens, Age trajectories, business.industry, Height, Weight, Body Height, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, ONSET, Ciências da Saúde, Ciências médicas e da saúde, School-aged children, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, terveysriskit, Estilos de Vida e Impacto na Saúde
Abstract: BACKGROUND: Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents., METHODS: For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence., FINDINGS: We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls., INTERPRETATION: The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks., Wellcome Trust, AstraZeneca Young Health Programme, EU., peer-reviewed
Published: 2020
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4. Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Author: Bixby, Honor, Bentham, James, Zhou, Bin, Di Cesare, Mariachiara, Paciorek, Christopher J., Bennett, James E., Taddei, Cristina, Stevens, Gretchen A., Rodriguez-Martinez, Andrea, Carrillo-Larco, Rodrigo M., Khang, Young-Ho, Soric, Maroje, Gregg, Edward W., Miranda, J. Jaime, Bhutta, Zulfiqar A., Savin, Stefan, Sophiea, Marisa K., Iurilli, Maria L. C., Solomon, Bethlehem D., Cowan, Melanie J., Riley, Leanne M., Danaei, Goodarz, Bovet, Pascal, Chirita-Emandi, Adela, Hambleton, Ian R., Hayes, Alison J., Ikeda, Nayu, Kengne, Andre P., Laxmaiah, Avula, Li, Yanping, McGarvey, Stephen T., Mostafa, Aya, Neovius, Martin, Starc, Gregor, Zainuddin, Ahmad A., Abarca-Gomez, Leandra, Abdeen, Ziad A., Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Hamid, Zargar Abdul, Garba, Jamila Abubakar, Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Agdeppa, Imelda A., Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Naser, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, AlBuhairan, Fadia, AlDhukair, Shahla, Al-Hazzaa, Hazzaa M., Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Al-Othman, Amani Rashed, Al-Raddadi, Rajaa, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Bo, Lars, Anderssen, Sigmund A., Angquist, Lars H., Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E., Arlappa, Nimmathota, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assuncao, Maria Cecilia F., Aung, May Soe, Auvinen, Juha, Avdicova, Maria, Azevedo, Ana, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V., Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L., Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, Jose R., Barbagallo, Carlo M., Barcelo, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V. G., Bata, Iqbal, Batieha, Anwar M., Batista, Rosangela L., Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Bel-Serrat, Silvia, Ben Romdhane, Habiba, Benedics, Judith, Benet, Mikhail, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Hongsheng, Bi, Yufang, Biehl, Anna, Lele, Elysee Claude Bika, Bikbov, Mukharram, Bista, Bihungum, Bjelica, Dusko J., Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Bjorkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M., Boehm, Bernhard O., Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bonaccio, Marialaura, Bongard, Vanina, Bopp, Matthias, Borchini, Rossana, Borghs, Herman, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn C. E., Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Breda, Joao, Brenner, Hermann, Brewster, Lizzy M., Brian, Garry R., Brinduse, Lacramioara, Bruno, Graziella, Bueno-de-Mesquita, H. Bas, Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, Cabrera de Leon, Antonio, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, Jose, Can, Gamze, Can, Gunay, Candido, Ana Paula C., Canete, Felicia, Capanzana, Mario V., Capuano, Eduardo, Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carmuega, Esteban, Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Celikcan, Ertugrul, Censi, Laura, Cesar, Juraci A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Rahim, Norsyamlina Che Abdul, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheng, Yiling J., Chetrit, Angela, Chikova-Iscener, Ekaterina, Chiolero, Arnaud, Chiou, Shu-Ti, Chirlaque, Maria-Dolores, Cho, Belong, Cho, Yumi, Christensen, Kaare, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cilia, Michelle, Cinteza, Eliza, Claessens, Frank, Clarke, Janine, Clays, Els, Concin, Hans, Confortin, Susana C., Cooper, Cyrus, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crampin, Amelia C., Crujeiras, Ana B., Cruz, Juan J., Cucu, Alexandra, Cui, Liufu, Dallongeville, Jean, Damasceno, Albertino, Damsgaard, Camilla T., Dankner, Rachel, Dantoft, Thomas M., D'Arrigo, Graziella, Dasgupta, Parasmani, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, De Curtis, Amalia, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, Karin, de Rooij, Susanne R., De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D., Dehghan, Abbas, Delisle, Helene, Delpeuch, Francis, Dennison, Elaine, Deschamps, Valerie, Dhana, Klodian, Dhimal, Meghnath, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Do, Ha T. P., Dobson, Annette J., Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P., Doering, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, d'Orsi, Eleonora, Doua, Kouamelan, Drygas, Wojciech, Duan, Jia Li, Duante, Charmaine A., Duda, Rosemary B., Duleva, Vesselka, Dulskiene, Virginija, Dumith, Samuel C., Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Egbagbe, Eruke E., Eggertsen, Robert, Eiben, Gabriele, Ekelund, Ulf, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elliott, Paul, Engle-Stone, Reina, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Escobedo-de la Pena, Jorge, Evans, Alun, Faeh, David, Fall, Caroline H., Sant'Angelo, Victoria Farrugia, Farzadfar, Farshad, Fattahi, Mohammad R., Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandes, Romulo A., Fernandez-Berges, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrer, Eldridge, Ferrieres, Jean, Fijalkowska, Anna, Fink, Gunther, Fischer, Krista, Flores, Eric Monterubio, Foeger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M., Francis, Damian K., Franco, Maria do Carmo, Franco, Oscar H., Frontera-Juan, Guillem, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Galeone, Daniela, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Gazzinelli, Andrea, Geiger, Harald, Geleijnse, Johanna M., Ghanbari, Ali, Ghasemi, Erfan, Ghasemian, Anoosheh, Gheorghe-Fronea, Oana-Florentina, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K., Giovannelli, Jonathan, Gironella, Glen, Giwercman, Aleksander, Godos, Justyna, Gogen, Sibel, Goldsmith, Rebecca A., Goltzman, David, Goncalves, Helen, Gonzalez, Angel R., Gonzalez-Chica, David A., Gonzalez-Gross, Marcela, Gonzalez-Leon, Margot, Gonzalez-Rivas, Juan P., Gonzalez-Villalpando, Maria-Elena, Gottrand, Frederic, Graca, Antonio Pedro, Graff-Iversen, Sidsel, Grafnetter, Dusan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grontved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Gu, Dongfeng, Gualdi-Russo, Emanuela, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc, Guo, Xiuhua, Guo, Yin, Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Hadjigeorgiou, Charalambos A., Haghshenas, Rosa, Halkjaer, Jytte, Hardy, Rebecca, Kumar, Rachakulla Hari, Hassapidou, Maria, Hata, Jun, Haugsgjerd, Teresa, He, Jiang, He, Yuna, Heidinger-Felso, Regina, Heinen, Mirjam, Hejgaard, Tatjana, Hendriks, Marleen Elisabeth, Henriques, Ana, Hernandez Cadena, Leticia, Herrala, Sauli, Herrera, Victor M., Herter-Aeberli, Isabelle, Heshmat, Ramin, Hill, Allan G., Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Hopman, Wilma M., Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, Jose Maria, Huhtaniemi, Ilpo Tapani, Petrescu, Constanta Huidumac, Huisman, Martijn, Husseini, Abdullatif, Chinh Nguyen Huu, Huybrechts, Inge, Hwalla, Nahla, Hyska, Jolanda, Iacoviello, Licia, Ibarluzea, Jesus M., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikram, M. 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A, Plans-Rubió P, Poh BK, Pohlabeln H, Pop RM, Popovic SR, Porta M, Portegies MLP, Posch G, Poulimeneas D, Pouraram H, Pourshams A, Poustchi H, Pradeepa R, Price AJ, Price JF, Puder JJ, Pudule I, Puhakka SE, Puiu M, Punab M, Qasrawi RF, Qorbani M, Quoc Bao T, Radhika MS, Radic I, Radisauskas R, Rahman M, Raitakari O, Raj M, Rajkumar H, Rakhmatulloev S, Ramachandra Rao S, Ramachandran A, Ramke J, Ramos E, Ramos R, Rampal L, Rampal S, Rao KM, Rascon-Pacheco RA, Rasmussen M, Redon J, Reganit PFM, Regecová V, Revilla L, Ribas-Barba L, Ribeiro R, Riboli E, Rigo F, Rinaldo N, Rinke de Wit TF, Rito A, Ritti-Dias RM, Rivera JA, Robitaille C, Rodrigues D, Rodríguez-Artalejo F, Rodriguez-Perez MC, Rodríguez-Villamizar LA, Rojas-Martinez R, Rojroongwasinkul N, Romaguera D, Rosengren A, Rouse I, Roy JGR, Rubinstein A, Rühli FJ, Ruidavets J-B, Ruiz Moreno E, Ruiz-Betancourt BS, Russo P, Rust P, Rutkowski M, Sabanayagam C, Sachdev HS, Safiri S, Saidi O, Salanave B, Salazar-Martinez E, Salmerón D, Salomaa V, Salonen JT, Salvetti M, Sánchez-Abanto J, Sandjaja, Sans S, Santa-Marina L, Santos DA, Santos IS, Santos O, Santos R, Sanz SS, Saramies JL, Sardinha LB, Sarrafzadegan N, Saum K-U, Savva S, Savy M, Scazufca M, Schaffrath Rosario A, Schargrodsky H, Schienkiewitz A, Schindler K, Schipf S, Schmidt CO, Schmidt IM, Schöttker B, Schultsz C, Schutte AE, Sebert S, Sein AA, Selamat R, Sember V, Sen A, Senbanjo IO, Sepanlou SG, Sequera V, Serra-Majem L, Servais J, Shalnova SA, Sharma SK, Shaw JE, Shengelia L, Shibuya K, Shimizu-Furusawa H, Shin DW, Shin Y, Siani A, Siantar R, Sibai AM, Silva AM, Silva DAS, Simon M, Simons J, Simons LA, Si-Ramlee K, Sjöberg A, Sjöström M, Slowikowska-Hilczer J, Slusarczyk P, Smeeth L, Snijder MB, So H-K, Sobngwi E, Söderberg S, Soekatri MYE, Soemantri A, Solfrizzi V, Sonestedt E, Song Y, Sørensen TIA, Sossa Jérome C, Soumaré A, Spinelli A, Spiroski I, Staessen JA, Stamm H, Stathopoulou MG, Staub K, Stavreski B, Steene-Johannessen J, Stehle P, Stein AD, Stergiou GS, Stessman J, Stöckl D, Stocks T, Stokwiszewski J, Stratton G, Stronks K, Strufaldi MW, Sturua L, Suárez-Medina R, Sun C-A, Sundström J, Sung Y-T, Sunyer J, Suriyawongpaisal P, Swinburn BA, Sy RG, Sylva RC, Szponar L, Tai ES, Tammesoo M-L, Tamosiunas A, Tan EJ, Tang X, Tanser F, Tao Y, Tarawneh MR, Tarp J, Tarqui-Mamani CB, Taxová Braunerová R, Taylor A, Tchibindat F, Tebar WR, Tell G, Tello T, Theobald H, Theodoridis X, Thijs L, Thuesen BH, Tichá L, Timmermans EJ, Tjonneland A, Tolonen HK, Tolstrup JS, Topbas M, Topór-Madry R, Tormo MJ, Tornaritis MJ, Torrent M, Toselli S, Traissac P, Trichopoulos D, Trichopoulou A, Trinh OTH, Trivedi A, Tsao Y-H, Tshepo L, Tsigga M, Tsugane S, Tulloch-Reid MK, Tullu F, Tuomainen T-P, Tuomilehto J, Turley ML, Tynelius P, Tzotzas T, Tzourio C, Ueda P, Ugel EE, Ukoli FAM, Ulmer H, Unal B, Uusitalo HMT, Vaitkeviciute J, Valdivia G, Vale S, Valvi D, van der Schouw YT, Van Herck K, Van Minh H, van Rossem L, Van Schoor NM, van Valkengoed IGM, Vanderschueren D, Vanuzzo D, Varela-Moreiras G, Varona-Pérez P, Vatten L, Vega T, Veidebaum T, Velasquez-Melendez G, Velika B, Veronesi G, Verschuren WMM, Victora CG, Viegi G, Viet L, Vineis P, Vioque J, Virtanen JK, Visser M, Visvikis-Siest S, Viswanathan B, Vlasoff T, Vollenweider P, Völzke H, Voutilainen A, Voutilainen S, Vrijheid M, Vrijkotte TGM, Wade AN, Wagner A, Waldhör T, Walton J, Wan Bebakar WM, Wan Mohamud WN, Wanderley RS, Jr, Wang M-D, Wang Q, Wang X, Wang YX, Wang Y-W, Wannamethee SG, Wareham N, Weber A, Weerasekera D, Weghuber D, Wei W, Whincup PH, Widhalm K, Widyahening IS, Wiecek A, Wijga AH, Wilks RJ, Willeit J, Willeit P, Wilsgaard T, Wojtyniak B, Wong JE, Wong TY, Wong-McClure RA, Woo J, Woodward M, Wu FC, Wu J, Wu S, Xu H, Xu L, Yamborisut U, Yan W, Yang L, Yang X, Yang Y, Yardim N, Yaseri M, Ye X, Yiallouros PK, Yngve A, Yoosefi M, Yoshihara A, You QS, You S-L, Younger-Coleman NO, Yusoff AF, Zaccagni L, Zafiropulos V, Zamani F, Zambon S, Zampelas A, Zamrazilová H, Zapata ME, Zaw KK, Zdrojewski T, Zeljkovic Vrkic T, Zeng Y, Zhao D, Zhao W, Zheng W, Zheng Y, Zholdin B, Zhou M, Zhu D, Zhussupov B, Zimmermann E, Zuñiga Cisneros J, Ezzati M, Yiallouros, Panayiotis K. [0000-0002-8339-9285], APH - Societal Participation & Health, APH - Aging & Later Life, Epidemiology and Data Science, Public and occupational health, APH - Health Behaviors & Chronic Diseases, and APH - Personalized Medicine
Subjects: Male, Rural Population, obesity, Obesity, body mass index, Settore MED/09 - Medicina Interna, Letter, Urban Population, Epidemiology, [SDV]Life Sciences [q-bio], humanos, body-mass index, adolescente, Geographic Mapping, Sex Factor, países desarrollados, Rural Health, purl.org/pe-repo/ocde/ford#3.03.09 [https], systematic analysis, Body Mass Index, países en desarrollo, 80 and over, risk factors, Age Factor, physical-activity, mediana edad, mapeo geográfico, Aged, 80 and over, anciano, purl.org/pe-repo/ocde/ford#3.02.18 [https], dieta, Age Factors, health, adulto, Middle Aged, Multidisciplinary Sciences, adulto joven, [SDV] Life Sciences [q-bio], estado nutricional, nutrition, Science & Technology - Other Topics, NUTRITION, Female, HEALTH, pooled analysis, Diet, Healthy, worldwide trends, Human, Developed Countrie, Adult, Adolescent, purl.org/pe-repo/ocde/ford#3.03.04 [https], FOOD SYSTEM, Socio-culturale, Nutritional Status, URBAN, Aged, Developed Countries, Developing Countries, Humans, Obesity, Sex Factors, Urban Health, Young Adult, POOLED ANALYSIS, Developing Countrie, MIDDLE-INCOME COUNTRIES, SYSTEMATIC ANALYSIS, Urban rural Obesity Body-Mass-Index, obesidad, Middle-income countries, food system, urban, weight, Healthy, Science & Technology, índice de masa corporal, Diet, PHYSICAL-ACTIVITY, WORLDWIDE TRENDS, Risk factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, WEIGHT
Abstract: Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories., This study was funded by the Wellcome Trust. H.B. was supported by a Medical Research Council Doctoral Training Partnership Studentship, J.B. by a Royal Society Research Grant, and M.D.C. by an Academy of Medical Sciences Springboard Award. We thank L. Jaacks, B. Popkin, S. Sundberg and W. Willett for recommendations of relevant citations. The authors are responsible for the views expressed in this Letter and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.
Published: 2019
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5. Investigating the associations between uncarboxylated matrix gla protein as a proxy for vitamin K status and cardiovascular disease risk factors in a general adult population.

Author: Lauridsen JA, Leth-Møller KB, Møllehave LT, Kårhus LL, Dantoft TM, Kofoed KF, and Linneberg A
Subjects: Humans, Middle Aged, Male, Female, Adult, Cross-Sectional Studies, Aged, Denmark epidemiology, Heart Disease Risk Factors, Young Adult, Risk Factors, Biomarkers blood, Vitamin K Deficiency blood, Vitamin K Deficiency complications, Nutritional Status, Matrix Gla Protein, Extracellular Matrix Proteins blood, Calcium-Binding Proteins blood, Vitamin K blood, Cardiovascular Diseases epidemiology, Cardiovascular Diseases blood
Abstract: Purpose: Vitamin K is an activator of vitamin K dependent proteins, one of which is the potent inhibitor of vascular calcification, matrix Gla protein (MGP). The purpose of this study is to investigate the association between an inverse proxy of functional vitamin K status, plasma dephospho-uncarboxylated MGP (dp-ucMGP), and cardiovascular disease risk factors (CVDRFs)., Methods: In a cross-sectional population-based health examination study of 4,092 individuals aged 24-77 years, the vitamin K status was assessed using plasma dp-ucMGP. All participants were linked to Danish National Prescription Register to obtain information on the use of vitamin K antagonists. The associations between log2 transformed dp-ucMGP values and CVDRFs were determined using regression models adjusted for sex, age, lifestyle factors, kidney function and waist circumference., Results: Higher dp-ucMGP levels were associated with increased risk of central obesity (Odds Ratio (OR) 4.76, 95% Confidence Intervals (CI) 3.57-6.34), diabetes (OR 1.96, 95% CI 1.11-3.45), hyperlipidaemia (OR 1.43, 95% CI 1.01-2.03), and impaired kidney function (OR 9.83, 95% CI 5.49-17.59) per doubling in dp-ucMGP. Dp-ucMGP was not independently associated with hypertension or arterial stiffness., Conclusion: Higher dp-ucMGP levels were associated with central obesity, diabetes, hyperlipidaemia, and impaired kidney function. Prospective studies and intervention studies examining the effects of improving vitamin K status are needed to clarify the potential role of vitamin K in relation to these CVDRFs., Competing Interests: Declarations. Conflict of interest: A. Linneberg has received an unrestricted grant and investigational products from Kappa Bioscience A/S for an intervention trial (The InterVitaminK Trial; clinicatrials.gov identifier NCT05259046) using vitamin K supplements as the active intervention. The remaining other authors declare no personal or financial conflict of interest., (© 2024. The Author(s).)
Published: 2024
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6. Maternal thyroid function in early pregnancy and offspring school performance and neurodevelopmental disorders.

Author: Møllehave LT, Grand MK, Kriegbaum M, Andersen CL, Lind BS, van Vliet NA, van Heemst D, and Strandberg-Larsen K
Abstract: Context: Thyroid hormones are critical for neural development, and during the first trimester of pregnancy the fetus relies fully on maternal thyroid hormone production., Objective: To investigate the associations between maternal thyroid hormone levels in the first trimester with the child's school performance, risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD)., Methods: From the Copenhagen Primary Care Laboratory Pregnancy Database information on first trimester TSH and fT4 measurements in mothers of children born in 2000-2014 were linked with information on the child's standardized test scores in school, ADHD (patient record diagnoses and medication) and ASD (patient record diagnoses) until end of 2018. Associations of TSH and fT4 with the outcomes were individually assessed by linear mixed models and Cox regression models. The analyses were stratified by preexisting maternal thyroid disorders., Results: TSH measurements were available for 17,909 mother-child dyads. Among those with children born in 2000-2009, 6,126 had a standardized school test score and were analyzed for the association between maternal thyroid hormone levels and child's school performance, and no support for an association was found. The association between thyroid hormone levels and child's risk of ADHD and ASD were analyzed for the 17,909 dyads and with no support for an association between thyroid hormone levels and these neurodevelopmental disorders. Stratification by preexisting maternal thyroid disorders did not affect the results., Conclusions: We found no evidence for associations between first trimester maternal thyroid hormone levels and child's school performance, or risk of ADHD or ASD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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7. Does iodine fortification affect the risk of atrial fibrillation in incident hyperthyroidism? A national register-based cohort.

Author: Møllehave LT, Knudsen N, Prescott E, Pedersen IB, Ravn-Haren G, Carlé A, and Linneberg A
Subjects: Humans, Comorbidity, Risk, Incidence, Risk Factors, Atrial Fibrillation epidemiology, Atrial Fibrillation etiology, Iodine, Hyperthyroidism complications, Hyperthyroidism epidemiology, Hyperthyroidism diagnosis
Abstract: Objective: Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, the sex-, age- and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate-mild iodine deficiency to low adequacy. DESIGN, PATIENTS AND MEASUREMENTS: Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997-2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities., Results: Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62-0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region., Conclusions: Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)
Published: 2024
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8. Cohort Profile Update: The Glostrup Population Studies 1964-2024.

Author: Møllehave LT, Madsen AL, Kampmann FB, Bjerregaard AA, Dantoft TM, Leth-Møller KB, Thysen SM, Schovsbo SU, Jacobsen RK, Aadahl M, Osler M, Jørgensen T, Linneberg A, and Kårhus LL
Subjects: Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Cohort Studies, Denmark, Population Health
Published: 2024
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9. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

Author: Sterenborg RBTM, Steinbrenner I, Li Y, Bujnis MN, Naito T, Marouli E, Galesloot TE, Babajide O, Andreasen L, Astrup A, Åsvold BO, Bandinelli S, Beekman M, Beilby JP, Bork-Jensen J, Boutin T, Brody JA, Brown SJ, Brumpton B, Campbell PJ, Cappola AR, Ceresini G, Chaker L, Chasman DI, Concas MP, Coutinho de Almeida R, Cross SM, Cucca F, Deary IJ, Kjaergaard AD, Echouffo Tcheugui JB, Ellervik C, Eriksson JG, Ferrucci L, Freudenberg J, Fuchsberger C, Gieger C, Giulianini F, Gögele M, Graham SE, Grarup N, Gunjača I, Hansen T, Harding BN, Harris SE, Haunsø S, Hayward C, Hui J, Ittermann T, Jukema JW, Kajantie E, Kanters JK, Kårhus LL, Kiemeney LALM, Kloppenburg M, Kühnel B, Lahti J, Langenberg C, Lapauw B, Leese G, Li S, Liewald DCM, Linneberg A, Lominchar JVT, Luan J, Martin NG, Matana A, Meima ME, Meitinger T, Meulenbelt I, Mitchell BD, Møllehave LT, Mora S, Naitza S, Nauck M, Netea-Maier RT, Noordam R, Nursyifa C, Okada Y, Onano S, Papadopoulou A, Palmer CNA, Pattaro C, Pedersen O, Peters A, Pietzner M, Polašek O, Pramstaller PP, Psaty BM, Punda A, Ray D, Redmond P, Richards JB, Ridker PM, Russ TC, Ryan KA, Olesen MS, Schultheiss UT, Selvin E, Siddiqui MK, Sidore C, Slagboom PE, Sørensen TIA, Soto-Pedre E, Spector TD, Spedicati B, Srinivasan S, Starr JM, Stott DJ, Tanaka T, Torlak V, Trompet S, Tuhkanen J, Uitterlinden AG, van den Akker EB, van den Eynde T, van der Klauw MM, van Heemst D, Verroken C, Visser WE, Vojinovic D, Völzke H, Waldenberger M, Walsh JP, Wareham NJ, Weiss S, Willer CJ, Wilson SG, Wolffenbuttel BHR, Wouters HJCM, Wright MJ, Yang Q, Zemunik T, Zhou W, Zhu G, Zöllner S, Smit JWA, Peeters RP, Köttgen A, Teumer A, and Medici M
Subjects: Humans, Genome-Wide Association Study, Triiodothyronine metabolism, Thyrotropin metabolism, Thyroid Gland metabolism, Thyroxine metabolism
Abstract: To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases., (© 2024. The Author(s).)
Published: 2024
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10. Author Correction: The power of genetic diversity in genome-wide association studies of lipids.

Author: Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Yousri NA, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung YJ, Chen S, Liu F, Yang J, Kentistou KA, Gorski M, Brumat M, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Xue C, Zhang J, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, Lee J, van der Laan SW, Chitrala KN, Weiss S, Zimmermann ME, Lee JY, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hildalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Schwander K, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Highland HM, Young KL, Kawaguchi T, Thiery J, Bis JC, Nadkarni GN, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, Bhatti KF, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Chen YE, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Kato N, Schulze MB, Girotto G, Jung B, Böger CA, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Yajnik CS, Mercader JM, Tusié-Luna T, Aguilar-Salinas CA, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Lu F, Qu J, Hishigaki H, Lin X, März W, Parra EJ, Cruz M, Gudnason V, Tardif JC, Lettre G, 't Hart LM, Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Psaty BM, Brandslund I, Pramstaller PP, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Cucca F, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Justice AE, Baras A, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Thorsteinsdottir U, Stefansson K, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Rotimi CN, Hazelhurst S, Ramsay M, Trembath RC, van Heel DA, Tamiya G, Yamamoto M, Kim BJ, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Natarajan P, Peloso GM, Brown CD, Morris AP, Assimes TL, Deloukas P, Sun YV, and Willer CJ
Published: 2023
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11. Z-scores of bone turnover markers calculated from new established sex- and age-specific reference curves are associated to future change in BMD in children and adolescents.

Author: Rand MS, Diemar SS, Møllehave LT, Heidemann M, Thuesen BH, Petersen JH, Johannesen J, Schou AJ, Wedderkopp N, Mølgaard C, and Jørgensen NR
Subjects: Humans, Child, Adolescent, Absorptiometry, Photon, Age Factors, Bone Density, Bone Remodeling
Abstract: Competing Interests: Declaration of competing interest None.
Published: 2023
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12. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Author: Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Nardone GG, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Liang J, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Mercader JM, Costanzo MC, Jang D, Burtt NP, Villalpando CG, Orozco L, Fornage M, Tai E, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Qu J, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, Hart LM', Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Chuang LM, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, Willemsen AHM, Cupples L, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen Y, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson PWF, Frayling TM, Hirschhorn JN, Kathiresan S, Mohlke KL, Sun YV, Morris AP, Boehnke M, Brown CD, Natarajan P, Deloukas P, Willer CJ, Assimes TL, and Peloso GM
Subjects: Humans, Sex Characteristics, Phenotype, Lipids genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Genome-Wide Association Study, Genetic Predisposition to Disease
Abstract: Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery., Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism., Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., (© 2022. The Author(s).)
Published: 2022
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13. Association between infections and functional somatic disorders: a cross-sectional population-based cohort study.

Author: Schovsbo SU, Møllehave LT, Petersen MW, Ahrendt Bjerregaard A, Eliasen M, Pedersen SB, Eplov LF, Kårhus LL, Fink P, Linneberg A, Dantoft TM, Jørgensen T, and Benros ME
Subjects: Male, Humans, Female, Cross-Sectional Studies, Cohort Studies, Retrospective Studies, Irritable Bowel Syndrome epidemiology, Chronic Pain
Abstract: Objectives: It has been suggested that infections can trigger functional somatic disorders (FSD). However, current evidence is limited by inconsistent findings in smaller studies conducted in clinical settings within selected populations and short follow-up times. We aimed to test the hypothesis that former infections are associated with FSD using data from nationwide registries and a large population-based cohort study, the Danish Study of Functional Disorders study., Design: FSD cases were identified in a cross-sectional population-based cohort and linked retrospectively to former hospital contacts with infections identified in the Danish National Patient Registry. The associations between FSD and former infections within 17 years were analysed using logistic regressions to calculate ORs and 95% CIs adjusted for age, sex and subjective social status., Setting: A population-based cohort in Denmark examined between 2011 and 2015., Participants: A total of 9656 men and women aged 18-76 years., Main Outcome Measures: FSD measured by various delimitations, including bodily distress syndrome (BDS), irritable bowel (IB), chronic fatigue (CF), chronic widespread pain (CWP), and multiple chemical sensitivity (MCS)., Results: Overall, infections were associated with increased risk of all delimitations of FSD. The associations were more pronounced for multisystemic FSD. The number of prior infections increased the risk in a dose-response manner (p<0.0001). Bacterial but not viral infections were significantly associated with BDS (OR 1.69 (95% CI 1.46 to 1.96)), IB (OR 1.41 (95% CI 1.06 to 1.88)), CWP (OR 1.47 (95% CI 1.13 to 1.90)) and CF (OR 1.62 (95% CI 1.34 to 1.96)), but not MCS., Conclusion: Former infections leading to hospital contacts were associated with a higher risk of having FSD. These associations were more pronounced for bacterial than viral infections, and more infections increased the risk in a dose-response manner. These results tend to support the idea that severe infections could play a role in FSD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2022
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14. Population-based epidemiology: The Glostrup Population Studies 1964-2021.

Author: Kårhus LL, Møllehave LT, Osler M, Jørgensen T, and Linneberg A
Subjects: Adult, Cohort Studies, Female, Humans, Life Style, Male, Surveys and Questionnaires, Aging, Research Design
Abstract: The Glostrup Population Studies are population-based cohorts undertaken in the south-western part of Greater Copenhagen since 1964. The participants were randomly selected from the adult general population. The first cohort was established to assess cardiovascular risk factors and, since, the objectives have been broadened to describe and analyse the health of the general population. The studies are health-examination studies with clinical and biochemical data in addition to data from self-administered questionnaires and, in some studies, interviews. Fasting blood and urine samples were collected and stored in our biobank for further studies. Several of the cohorts were performed according to standardized methods in international consortia, hence data have been pooled with other, both Danish and international, cohorts. To date more than 30,000 individuals, both men and women, aged 15-85 years, have participated in The Glostrup Population Studies and participants have been re-examined up to eight times. The data can be used for disease-specific epidemiology, social epidemiology, genetic epidemiology, ageing, lifestyle and health interventions nested within the cohorts. The Glostrup Population Studies represent a great resource; the possibility of merging the different cohorts enables large datasets, as well as trends over time. Furthermore, the long follow-up in both the national registers and with follow-up examinations is unique. The purpose of this commentary is to inform about The Glostrup Population Studies and to invite collaborations to continue utilizing this great resource to combat current and future challenges within health promotion and disease prevention.
Published: 2022
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15. Socioeconomic influence on treatment with liothyronine and desiccated thyroid extract in Denmark.

Author: la Cour JL, Møllehave LT, Medici BR, Jensen CZ, Bjerregaard AA, and Nygaard B
Abstract: Introduction: High compared with low educational level increases the odds of starting levothyroxine (L-T4) with a normal thyroid-stimulating hormone - the mechanism is most likely patient request. The use of liothyronine (L-T3) and desiccated thyroid extract (DTE) is also speculated to be initiated at patients' request. Therefore, the primary aim of this study was to evaluate if educational level influences treatment with L-T3 and DTE., Material and Methods: In this register-based cross-sectional study, we included all Danish citizens ≥30 years with redeemed prescription of L-T4, L-T3, or DTE during 2017-2020. We defined educational levels as short, medium, and long (<10 years, 10-12 years, and above 12 years, respectively). The association between educational level and treatment with LT3 or DTE vs only LT4 was analyzed in logistic regression models adjusted for age and sex., Results: We included 154,360 individuals using thyroid medication of whom 3829 were treated with L-T3 (2.48%) and 430 with DTE (0.28%). The usage was highest among women (3.15%) and the age group 40-49 (5.6%). Longer education compared with short increased the odds of being treated with DTE or L-T3 (medium education odds ratio (OR) 1.61 (95% CI 1.50-1.8) and long education OR 1.95 (95% CI 1.79-2.13)). Test for trend: OR: 1.37 (95% CI 1.31-1.42). Adjustment for other covariates did not affect the results substantially., Conclusion: Persons with a longer compared to a shorter education are more often treated with either DTE or L-T3, and the usage of these drugs is limited to less than 3% of thyroid hormone users.
Published: 2022
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16. A saturated map of common genetic variants associated with human height.

Author: Yengo L, Vedantam S, Marouli E, Sidorenko J, Bartell E, Sakaue S, Graff M, Eliasen AU, Jiang Y, Raghavan S, Miao J, Arias JD, Graham SE, Mukamel RE, Spracklen CN, Yin X, Chen SH, Ferreira T, Highland HH, Ji Y, Karaderi T, Lin K, Lüll K, Malden DE, Medina-Gomez C, Machado M, Moore A, Rüeger S, Sim X, Vrieze S, Ahluwalia TS, Akiyama M, Allison MA, Alvarez M, Andersen MK, Ani A, Appadurai V, Arbeeva L, Bhaskar S, Bielak LF, Bollepalli S, Bonnycastle LL, Bork-Jensen J, Bradfield JP, Bradford Y, Braund PS, Brody JA, Burgdorf KS, Cade BE, Cai H, Cai Q, Campbell A, Cañadas-Garre M, Catamo E, Chai JF, Chai X, Chang LC, Chang YC, Chen CH, Chesi A, Choi SH, Chung RH, Cocca M, Concas MP, Couture C, Cuellar-Partida G, Danning R, Daw EW, Degenhard F, Delgado GE, Delitala A, Demirkan A, Deng X, Devineni P, Dietl A, Dimitriou M, Dimitrov L, Dorajoo R, Ekici AB, Engmann JE, Fairhurst-Hunter Z, Farmaki AE, Faul JD, Fernandez-Lopez JC, Forer L, Francescatto M, Freitag-Wolf S, Fuchsberger C, Galesloot TE, Gao Y, Gao Z, Geller F, Giannakopoulou O, Giulianini F, Gjesing AP, Goel A, Gordon SD, Gorski M, Grove J, Guo X, Gustafsson S, Haessler J, Hansen TF, Havulinna AS, Haworth SJ, He J, Heard-Costa N, Hebbar P, Hindy G, Ho YA, Hofer E, Holliday E, Horn K, Hornsby WE, Hottenga JJ, Huang H, Huang J, Huerta-Chagoya A, Huffman JE, Hung YJ, Huo S, Hwang MY, Iha H, Ikeda DD, Isono M, Jackson AU, Jäger S, Jansen IE, Johansson I, Jonas JB, Jonsson A, Jørgensen T, Kalafati IP, Kanai M, Kanoni S, Kårhus LL, Kasturiratne A, Katsuya T, Kawaguchi T, Kember RL, Kentistou KA, Kim HN, Kim YJ, Kleber ME, Knol MJ, Kurbasic A, Lauzon M, Le P, Lea R, Lee JY, Leonard HL, Li SA, Li X, Li X, Liang J, Lin H, Lin SY, Liu J, Liu X, Lo KS, Long J, Lores-Motta L, Luan J, Lyssenko V, Lyytikäinen LP, Mahajan A, Mamakou V, Mangino M, Manichaikul A, Marten J, Mattheisen M, Mavarani L, McDaid AF, Meidtner K, Melendez TL, Mercader JM, Milaneschi Y, Miller JE, Millwood IY, Mishra PP, Mitchell RE, Møllehave LT, Morgan A, Mucha S, Munz M, Nakatochi M, Nelson CP, Nethander M, Nho CW, Nielsen AA, Nolte IM, Nongmaithem SS, Noordam R, Ntalla I, Nutile T, Pandit A, Christofidou P, Pärna K, Pauper M, Petersen ERB, Petersen LV, Pitkänen N, Polašek O, Poveda A, Preuss MH, Pyarajan S, Raffield LM, Rakugi H, Ramirez J, Rasheed A, Raven D, Rayner NW, Riveros C, Rohde R, Ruggiero D, Ruotsalainen SE, Ryan KA, Sabater-Lleal M, Saxena R, Scholz M, Sendamarai A, Shen B, Shi J, Shin JH, Sidore C, Sitlani CM, Slieker RC, Smit RAJ, Smith AV, Smith JA, Smyth LJ, Southam L, Steinthorsdottir V, Sun L, Takeuchi F, Tallapragada DSP, Taylor KD, Tayo BO, Tcheandjieu C, Terzikhan N, Tesolin P, Teumer A, Theusch E, Thompson DJ, Thorleifsson G, Timmers PRHJ, Trompet S, Turman C, Vaccargiu S, van der Laan SW, van der Most PJ, van Klinken JB, van Setten J, Verma SS, Verweij N, Veturi Y, Wang CA, Wang C, Wang L, Wang Z, Warren HR, Bin Wei W, Wickremasinghe AR, Wielscher M, Wiggins KL, Winsvold BS, Wong A, Wu Y, Wuttke M, Xia R, Xie T, Yamamoto K, Yang J, Yao J, Young H, Yousri NA, Yu L, Zeng L, Zhang W, Zhang X, Zhao JH, Zhao W, Zhou W, Zimmermann ME, Zoledziewska M, Adair LS, Adams HHH, Aguilar-Salinas CA, Al-Mulla F, Arnett DK, Asselbergs FW, Åsvold BO, Attia J, Banas B, Bandinelli S, Bennett DA, Bergler T, Bharadwaj D, Biino G, Bisgaard H, Boerwinkle E, Böger CA, Bønnelykke K, Boomsma DI, Børglum AD, Borja JB, Bouchard C, Bowden DW, Brandslund I, Brumpton B, Buring JE, Caulfield MJ, Chambers JC, Chandak GR, Chanock SJ, Chaturvedi N, Chen YI, Chen Z, Cheng CY, Christophersen IE, Ciullo M, Cole JW, Collins FS, Cooper RS, Cruz M, Cucca F, Cupples LA, Cutler MJ, Damrauer SM, Dantoft TM, de Borst GJ, de Groot LCPGM, De Jager PL, de Kleijn DPV, Janaka de Silva H, Dedoussis GV, den Hollander AI, Du S, Easton DF, Elders PJM, Eliassen AH, Ellinor PT, Elmståhl S, Erdmann J, Evans MK, Fatkin D, Feenstra B, Feitosa MF, Ferrucci L, Ford I, Fornage M, Franke A, Franks PW, Freedman BI, Gasparini P, Gieger C, Girotto G, Goddard ME, Golightly YM, Gonzalez-Villalpando C, Gordon-Larsen P, Grallert H, Grant SFA, Grarup N, Griffiths L, Gudnason V, Haiman C, Hakonarson H, Hansen T, Hartman CA, Hattersley AT, Hayward C, Heckbert SR, Heng CK, Hengstenberg C, Hewitt AW, Hishigaki H, Hoyng CB, Huang PL, Huang W, Hunt SC, Hveem K, Hyppönen E, Iacono WG, Ichihara S, Ikram MA, Isasi CR, Jackson RD, Jarvelin MR, Jin ZB, Jöckel KH, Joshi PK, Jousilahti P, Jukema JW, Kähönen M, Kamatani Y, Kang KD, Kaprio J, Kardia SLR, Karpe F, Kato N, Kee F, Kessler T, Khera AV, Khor CC, Kiemeney LALM, Kim BJ, Kim EK, Kim HL, Kirchhof P, Kivimaki M, Koh WP, Koistinen HA, Kolovou GD, Kooner JS, Kooperberg C, Köttgen A, Kovacs P, Kraaijeveld A, Kraft P, Krauss RM, Kumari M, Kutalik Z, Laakso M, Lange LA, Langenberg C, Launer LJ, Le Marchand L, Lee H, Lee NR, Lehtimäki T, Li H, Li L, Lieb W, Lin X, Lind L, Linneberg A, Liu CT, Liu J, Loeffler M, London B, Lubitz SA, Lye SJ, Mackey DA, Mägi R, Magnusson PKE, Marcus GM, Vidal PM, Martin NG, März W, Matsuda F, McGarrah RW, McGue M, McKnight AJ, Medland SE, Mellström D, Metspalu A, Mitchell BD, Mitchell P, Mook-Kanamori DO, Morris AD, Mucci LA, Munroe PB, Nalls MA, Nazarian S, Nelson AE, Neville MJ, Newton-Cheh C, Nielsen CS, Nöthen MM, Ohlsson C, Oldehinkel AJ, Orozco L, Pahkala K, Pajukanta P, Palmer CNA, Parra EJ, Pattaro C, Pedersen O, Pennell CE, Penninx BWJH, Perusse L, Peters A, Peyser PA, Porteous DJ, Posthuma D, Power C, Pramstaller PP, Province MA, Qi Q, Qu J, Rader DJ, Raitakari OT, Ralhan S, Rallidis LS, Rao DC, Redline S, Reilly DF, Reiner AP, Rhee SY, Ridker PM, Rienstra M, Ripatti S, Ritchie MD, Roden DM, Rosendaal FR, Rotter JI, Rudan I, Rutters F, Sabanayagam C, Saleheen D, Salomaa V, Samani NJ, Sanghera DK, Sattar N, Schmidt B, Schmidt H, Schmidt R, Schulze MB, Schunkert H, Scott LJ, Scott RJ, Sever P, Shiroma EJ, Shoemaker MB, Shu XO, Simonsick EM, Sims M, Singh JR, Singleton AB, Sinner MF, Smith JG, Snieder H, Spector TD, Stampfer MJ, Stark KJ, Strachan DP, 't Hart LM, Tabara Y, Tang H, Tardif JC, Thanaraj TA, Timpson NJ, Tönjes A, Tremblay A, Tuomi T, Tuomilehto J, Tusié-Luna MT, Uitterlinden AG, van Dam RM, van der Harst P, Van der Velde N, van Duijn CM, van Schoor NM, Vitart V, Völker U, Vollenweider P, Völzke H, Wacher-Rodarte NH, Walker M, Wang YX, Wareham NJ, Watanabe RM, Watkins H, Weir DR, Werge TM, Widen E, Wilkens LR, Willemsen G, Willett WC, Wilson JF, Wong TY, Woo JT, Wright AF, Wu JY, Xu H, Yajnik CS, Yokota M, Yuan JM, Zeggini E, Zemel BS, Zheng W, Zhu X, Zmuda JM, Zonderman AB, Zwart JA, Chasman DI, Cho YS, Heid IM, McCarthy MI, Ng MCY, O'Donnell CJ, Rivadeneira F, Thorsteinsdottir U, Sun YV, Tai ES, Boehnke M, Deloukas P, Justice AE, Lindgren CM, Loos RJF, Mohlke KL, North KE, Stefansson K, Walters RG, Winkler TW, Young KL, Loh PR, Yang J, Esko T, Assimes TL, Auton A, Abecasis GR, Willer CJ, Locke AE, Berndt SI, Lettre G, Frayling TM, Okada Y, Wood AR, Visscher PM, and Hirschhorn JN
Subjects: Humans, Gene Frequency genetics, Genome, Human genetics, Genome-Wide Association Study, Haplotypes genetics, Linkage Disequilibrium genetics, Europe ethnology, Sample Size, Phenotype, Body Height genetics, Polymorphism, Single Nucleotide genetics, Chromosome Mapping
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)
Published: 2022
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17. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

Author: Ramdas S, Judd J, Graham SE, Kanoni S, Wang Y, Surakka I, Wenz B, Clarke SL, Chesi A, Wells A, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Lee WJ, Hsiung CA, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Schönherr S, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Le P, Feitosa MF, Wojczynski MK, Hemerich D, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Noah TL, Verma A, Slieker RC, Lo KS, Zilhao NR, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Emmel C, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Sankareswaran A, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Morgan A, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, He KY, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Ida Chen YD, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Walker M, Scott LJ, Koistinen HA, Chandak GR, Mercader JM, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Lu F, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, T Hart LM, Elders PJM, Rader DJ, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney L, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, Willems van Dijk K, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Huey-Herng Sheu W, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ikram A, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Tuomilehto J, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen YE, Ho YL, Lynch JA, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Struan Grant, Natarajan P, Sun YV, Morris AP, Deloukas P, Peloso G, Assimes TL, Willer CJ, Zhu X, and Brown CD
Subjects: Chromatin genetics, Genomics, Humans, Lipids genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract: A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology., Competing Interests: Declaration of interests G.C.-P. is currently an employee of 23andMe Inc. M.J.C. is the Chief Scientist for Genomics England, a UK Government company. B.M. Psaty serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. G. Thorleifsson, A.H., D.F.G., H. Holm, U.T., and K.S. are employees of deCODE/Amgen Inc. V.S. has received honoraria for consultations from Novo Nordisk and Sanofi and has an ongoing research collaboration with Bayer Ltd. M. McCarthy has served on advisory panels for Pfizer, NovoNordisk, and Zoe Global and has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. M. McCarthy and A. Mahajan are employees of Genentech and holders of Roche stock. M.S. receives funding from Pfizer Inc. for a project unrelated to this work. M.E.K. is employed by SYNLAB MVZ Mannheim GmbH. W.M. has received grants from Siemens Healthineers, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants from Astrazeneca, grants and personal fees from Sanofi, grants and personal fees from Alexion Pharmaceuticals, grants and personal fees from BASF, grants and personal fees from Abbott Diagnostics, grants and personal fees from Numares AG, grants and personal fees from Berlin-Chemie, grants and personal fees from Akzea Therapeutics, grants from Bayer Vital GmbH , grants from bestbion dx GmbH, grants from Boehringer Ingelheim Pharma GmbH Co KG, grants from Immundiagnostik GmbH, grants from Merck Chemicals GmbH, grants from MSD Sharp and Dohme GmbH, grants from Novartis Pharma GmbH, grants from Olink Proteomics, and other from Synlab Holding Deutschland GmbH, all outside the submitted work. A.V.K. has served as a consultant to Sanofi, Medicines Company, Maze Pharmaceuticals, Navitor Pharmaceuticals, Verve Therapeutics, Amgen, and Color Genomics; received speaking fees from Illumina and the Novartis Institute for Biomedical Research; received sponsored research agreements from the Novartis Institute for Biomedical Research and IBM Research, and reports a patent related to a genetic risk predictor (20190017119). S. Kathiresan is an employee of Verve Therapeutics and holds equity in Verve Therapeutics, Maze Therapeutics, Catabasis, and San Therapeutics. He is a member of the scientific advisory boards for Regeneron Genetics Center and Corvidia Therapeutics; he has served as a consultant for Acceleron, Eli Lilly, Novartis, Merck, Novo Nordisk, Novo Ventures, Ionis, Alnylam, Aegerion, Haug Partners, Noble Insights, Leerink Partners, Bayer Healthcare, Illumina, Color Genomics, MedGenome, Quest, and Medscape; and he reports patents related to a method of identifying and treating a person having a predisposition to or afflicted with cardiometabolic disease (20180010185) and a genetics risk predictor (20190017119). D.K. accepts consulting fees from Regeneron Pharmaceuticals. D.O.M.-K. is a part-time clinical research consultant for Metabolon, Inc. D. Saleheen has received support from the British Heart Foundation, Pfizer, Regeneron, Genentech, and Eli Lilly pharmaceuticals. P.N. reports investigator-initated grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis, personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis, Roche / Genentech, is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, geneXwell, and TenSixteen Bio, and spousal employment at Vertex, all unrelated to the present work. The spouse of C.J.W. is employed by Regeneron., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2022
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18. Risk-Benefit Assessment of an Increase in the Iodine Fortification Level of Foods in Denmark-A Pilot Study.

Author: Jakobsen LS, Nielsen JO, Paulsen SE, Outzen M, Linneberg A, Møllehave LT, Christensen T, and Ravn-Haren G
Abstract: Iodine deficiency is one of the most common nutritional disorders worldwide. In Denmark, the mandatory iodine fortification of salt of 13 ppm was introduced in 2000 to eradicate mild to moderate iodine deficiency and the fortification level was increased to 20 ppm in 2019. However, the optimal iodine intake is a narrow interval, and the risk of disease increases with intakes both below and above this interval. In this study, we quantified the risk-benefit balance in the Danish adult population by increasing the mandatory fortification level. We applied a risk-benefit assessment approach in which population-level iodine intakes before and after the increase in fortification were integrated with epidemiological evidence of the association between iodine nutrition status and risk of relevant diseases to estimate the number of cases caused or prevented and estimated health impact in terms of disability-adjusted life years (DALY). We estimated an overall beneficial health impact and prevention of 34.9 (95% UI: -51.6; -21.7) DALY per 100,000 adults in the population annually with the increase in fortification level. Prevention of low IQ in children due to maternal iodine deficiency was the primary contributor to overall health gain. The gain in healthy life years comes at the expense of extra cases of goiter due to iodine excess. Due to lack of data, hypo- and hyperthyroidism related to iodine status were not included. Neither were children as a population group. Because of this, as well as uncertainties inherent in the model and data used, results should be interpreted with caution. We argue that nation-specific, quantitative assessments of the public health impact of fortification programs provide transparent, evidence-based decision support. Future research should aim to enable the inclusion of all relevant health effects as well as children in the assessment.
Published: 2022
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19. Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting.

Author: Kårhus LL, Kriegbaum M, Grand MK, Lind BS, Møllehave LT, Rumessen JJ, Andersen CL, and Linneberg A
Subjects: Autoantibodies, Delayed Diagnosis, Female, Ferritins, Folic Acid, Gliadin, Humans, Immunoglobulin A, Immunoglobulin G, Male, Primary Health Care, Sensitivity and Specificity, Transglutaminases, Vitamin B 12, Celiac Disease
Abstract: To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000-2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD., (© 2022. The Author(s).)
Published: 2022
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20. Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Author: Møllehave LT, Eliasen MH, Strēle I, Linneberg A, Moreno-Reyes R, Ivanova LB, Kusić Z, Erlund I, Ittermann T, Nagy EV, Gunnarsdottir I, Arbelle JE, Troen AM, Pīrāgs V, Dahl L, Hubalewska-Dydejczyk A, Trofimiuk-Müldner M, de Castro JJ, Marcelino M, Gaberšček S, Zaltel K, Puig-Domingo M, Vila L, Manousou S, Nyström HF, Zimmermann MB, Mullan KR, Woodside JV, Völzke H, and Thuesen BH
Abstract: Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs., Design: Register-based cross-sectional study., Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated., Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs., Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.
Published: 2022
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21. The power of genetic diversity in genome-wide association studies of lipids.

Author: Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Yousri NA, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung YJ, Chen S, Liu F, Yang J, Kentistou KA, Gorski M, Brumat M, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Xue C, Zhang J, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, Lee J, van der Laan SW, Chitrala KN, Weiss S, Zimmermann ME, Lee JY, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hildalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Schwander K, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Highland HM, Young KL, Kawaguchi T, Thiery J, Bis JC, Nadkarni GN, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, Bhatti KF, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Chen YE, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Kato N, Schulze MB, Girotto G, Jung B, Böger CA, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Yajnik CS, Mercader JM, Tusié-Luna T, Aguilar-Salinas CA, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Lu F, Qu J, Hishigaki H, Lin X, März W, Parra EJ, Cruz M, Gudnason V, Tardif JC, Lettre G, 't Hart LM, Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Psaty BM, Brandslund I, Pramstaller PP, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Cucca F, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Justice AE, Baras A, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Thorsteinsdottir U, Stefansson K, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Rotimi CN, Hazelhurst S, Ramsay M, Trembath RC, van Heel DA, Tamiya G, Yamamoto M, Kim BJ, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Natarajan P, Peloso GM, Brown CD, Morris AP, Assimes TL, Deloukas P, Sun YV, and Willer CJ
Subjects: Genetic Predisposition to Disease genetics, Humans, Linkage Disequilibrium, Multifactorial Inheritance, Polymorphism, Single Nucleotide genetics, Population Groups, Cardiovascular Diseases genetics, Genome-Wide Association Study methods
Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2021
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22. Influence of educational level on test and treatment for incident hypothyroidism.

Author: Møllehave LT, Jacobsen RK, Linneberg A, Skaaby T, Knudsen N, Jørgensen T, Kårhus LL, Kriegbaum M, Grand MK, Siersma V, Lind B, Andersen CL, Nygaard B, Medici BB, Pedersen IB, Ravn-Haren G, and Thuesen BH
Subjects: Humans, Risk, Thyroid Function Tests, Thyroxine therapeutic use, Hypothyroidism diagnosis, Hypothyroidism drug therapy, Thyrotropin
Abstract: Objective: The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)-measurement and initiation of levothyroxine treatment., Design: Citizens in the greater Copenhagen Area during 2001-2015 were included. Individual-level data on educational level, diagnoses, GP-contact, TSH-measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH-measurement and treatment initiation following a TSH-measurement were analysed in Poisson regression models with generalized estimation equations., Results: A TSH-measurement was performed in 19% of 9,390,052 person years. The probability of TSH-measurement was higher with short (RR 1.16 [95% CI 1.15-1.16]) and medium (RR 1.11 [95% CI 1.06-1.12]) compared with long education. Treatment was initiated after 0.8% of 2,049,888 TSH-measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39-0.57) and 0.78 (95%CI 0.67-0.91) for short and medium compared with long education. For TSH 5-10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02-1.12) for short and 1.08 (95% CI 1.03-1.13) for medium compared with long education., Conclusion: The probability of TSH-measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short-medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education., (© 2021 John Wiley & Sons Ltd.)
Published: 2021
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23. Reference intervals in Danish children and adolescents for bone turnover markers carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP).

Author: Diemar SS, Lylloff L, Rønne MS, Møllehave LT, Heidemann M, Thuesen BH, Johannesen J, Schou AJ, Husby S, Wedderkopp N, Mølgaard C, and Jørgensen NR
Subjects: Adolescent, Biomarkers, Bone Remodeling, Child, Denmark, Female, Humans, Male, Osteocalcin, Peptide Fragments, Procollagen, Alkaline Phosphatase, Collagen Type I
Abstract: Purpose: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents., Method: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded., Results: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. β-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI., Conclusion: RI for β-CTX, PINP, OC and bone ALP varies with age and sex. β-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI., (Copyright © 2021 Elsevier Inc. All rights reserved.)
Published: 2021
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24. Symptoms and biomarkers associated with undiagnosed celiac seropositivity.

Author: Kårhus LL, Petersen J, Leth-Møller KB, Møllehave LT, Madsen AL, Thuesen BH, Schwarz P, Rumessen JJ, and Linneberg A
Subjects: Autoantibodies, Biomarkers, Female, Gliadin, Humans, Immunoglobulin A, Immunoglobulin G, Male, Transglutaminases, Celiac Disease diagnosis, Celiac Disease epidemiology, Delayed Diagnosis
Abstract: Background: Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease., Methods: We screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976-2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants., Results: We excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol (< 5 mmol/L) and low hemoglobin (< 7.3 mmol/L for women and < 8.3 mmol/L for men)., Conclusion: In this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.
Published: 2021
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25. Uncarboxylated matrix Gla-protein: A biomarker of vitamin K status and cardiovascular risk.

Author: Jespersen T, Møllehave LT, Thuesen BH, Skaaby T, Rossing P, Toft U, Jørgensen NR, Corfixen BL, Jakobsen J, Frimodt-Møller M, and Linneberg A
Subjects: Adult, Aged, Biomarkers blood, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Denmark epidemiology, Female, Heart Disease Risk Factors, Humans, Male, Middle Aged, Obesity, Odds Ratio, Vascular Calcification blood, Vitamin K Deficiency complications, Young Adult, Matrix Gla Protein, Calcium-Binding Proteins blood, Cardiovascular Diseases blood, Extracellular Matrix Proteins blood, Vitamin K Deficiency blood
Abstract: Background: Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) is a biomarker of functional vitamin K status. High plasma dp-ucMGP concentrations reflect a low vitamin K status and have been related to vascular calcification. Our aims were to assess plasma levels of dp-ucMGP and their association with cardiovascular risk in a general population., Methods: Plasma dp-ucMGP measurements were performed using the IDS-iSYS InaKtif MGP assay in 491 consecutive participants in a Danish general population study (229 males and 262 females, aged 19-71 years). Multivariable linear and logistic regressions were used to assess the association between dp-ucMGP levels and cardiovascular risk factors., Results: Mean ± standard deviation (SD) for dp-ucMGP was 465 ± 181 pmol/L, and upper 95th percentile was 690 pmol/L. In logistic regression analyses, an increase in dp-ucMGP category (<300, 300-399, 400-499, ≥500 pmol/L) was positively associated with obesity, odds ratio (OR) 2.27 (95% confidence interval (CI) 1.54-3.33), history of cardiovascular disease, OR 1.77 (CI 1.02-3.05), and above-median estimated pulse wave velocity (ePWV), OR 1.54 (CI 1.21-1.96), when adjusted for age, sex, and lifestyle factors. 1 SD increase in diastolic and systolic blood pressure (BP) corresponded to a 5.5% (CI 2.9-8.0%) and 4.7% (CI 2.1-7.4%) increase in dp-ucMGP, respectively, when adjusted for age and sex., Conclusion: Plasma dp-ucMGP levels were positively associated with obesity, BP, ePWV, and history of cardiovascular disease. These findings support that dp-ucMGP is a biomarker of cardiovascular risk, and that vitamin K status could play a role in vascular calcification. The strong association with obesity deserves further attention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
Published: 2020
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26. The association of thyroid stimulation hormone levels with incident ischemic heart disease, incident stroke, and all-cause mortality.

Author: Møllehave LT, Skaaby T, Linneberg A, Knudsen N, Jørgensen T, and Thuesen BH
Subjects: Female, Humans, Male, Mortality, Risk Factors, Thyroid Hormones, Myocardial Ischemia epidemiology, Stroke epidemiology, Thyrotropin blood
Abstract: Purpose: Thyroid dysfunction may affect the risk of cardiovascular disease and mortality through effects on myocardial and vascular tissue and metabolism. Levels of thyroid stimulating hormone (TSH) indicates thyroid function. We aimed to assess the association between TSH-levels and incident ischemic heart disease (IHD), incident stroke, and all-cause mortality., Methods: We included 13,865 participants (18-71 years, 51.6% women) from five cohort studies conducted during 1974-2008 were included. TSH was measured at the baseline examination and classified as <0.4; 0.4-2.5 (ref.); 2.5-5.0; 5.0-10, or >10 mU/l. Incident IHD, incident stroke, and all-cause mortality were identified in registries until ultimo 2013. Data were analysed by multivariate Cox regression with age as underlying time axis. Results from the individual cohorts were pooled by random-effects meta-analysis., Results: The crude incidence rate was for IHD 7.8 cases/1000 person years (PY); stroke 5.4 cases/1000 PY; and all-cause mortality 11.3 deaths/1000 PY (mean follow-up: 14 years). Analyses showed no statistically significant associations between TSH-levels and incident IHD or incident stroke in the partly or fully adjusted models. There was a statistically significant association between TSH of 2.5-5 mU/l and all-cause mortality (hazard ratio 1.145 (95% CI 1.004-1.306) compared with TSH of 0.4-2.5 mU/l in the fully adjusted model., Conclusion: The results do not provide evidence of a harmful effect of decreased or increased TSH on IHD or stroke in the general population. However, there is some indication of an elevated risk for all-cause mortality with TSH 2.5-5 mU/l compared with 0.4-2.5 mU/l.
Published: 2020
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27. Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase-reference intervals and confounders for two bone formation markers.

Author: Diemar SS, Møllehave LT, Quardon N, Lylloff L, Thuesen BH, Linneberg A, and Jørgensen NR
Subjects: Adult, Aged, Biomarkers blood, Bone Remodeling, Bone and Bones metabolism, Female, Follow-Up Studies, Humans, Male, Middle Aged, Osteogenesis, Reference Values, Young Adult, Age Factors, Alkaline Phosphatase blood, Osteocalcin blood, Sex Factors
Abstract: Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers., Objective: The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population., Methods: Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24-76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included., Results: The geometric mean and 95%RI for bone ALP were 13.9 μg/L (7.6-25.6) for men and 13.8 μg/L (7.0-27.4) for women, while for OC 16.0 μg/L (7.5-34.4) for men and 18.6 μg/L (8.1-42.9) for women. Levels of bone ALP increased with increasing age (β 1.004, p < 0.001), while female sex had no effect. OC levels decreased with increasing age (β 0.998, p = 0.009) and increased with female sex (β 1.104, p < 0.001). Based on our findings, we propose for bone ALP and OC three clinical RIs for men based on age and three clinical RI for women based on age and menopausal status., Conclusion: The RI for bone ALP and OC varies with age and sex and the BTMs are influenced differently by the two factors. Consequently, the need for establishing valid RIs is of great importance before the full potential of BTM can be used in clinical practice.
Published: 2020
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28. Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

Author: Skaaby T, Kilpeläinen TO, Taylor AE, Mahendran Y, Wong A, Ahluwalia TS, Paternoster L, Trompet S, Stott DJ, Flexeder C, Zhou A, Brusselle G, Sajjad A, Lahousse L, Tiemeier H, Have CT, Thuesen BH, Kårhus LL, Møllehave LT, Leth-Møller KB, Shabanzadeh DM, Gonzalez-Quintela A, Power C, Hyppönen E, Kuh D, Hardy R, Meitinger T, Jukema JW, Völker U, Nauck M, Völzke H, Friedrich N, Bonten TN, Noordam R, Mook-Kanamori DO, Tolstrup JS, Taube C, Peters A, Grallert H, Strauch K, Schulz H, Grarup N, Hansen T, Pedersen O, Burgess S, Munafò MR, and Linneberg A
Subjects: Adolescent, Aged, 80 and over, Alcohol Dehydrogenase genetics, Alcohol Drinking epidemiology, Asthma epidemiology, Denmark epidemiology, Female, Genotype, Humans, Hypersensitivity epidemiology, Immunoglobulin E metabolism, Male, Mendelian Randomization Analysis, Respiratory Function Tests, Rhinitis, Allergic, Seasonal epidemiology, Rhinitis, Allergic, Seasonal etiology, Young Adult, Alcohol Drinking adverse effects, Asthma etiology, Hypersensitivity etiology
Abstract: Aims: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E., Design: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions., Setting: Europe., Participants: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015., Measurements: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples., Findings: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI = 0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE., Conclusions: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal., (© 2018 Society for the Study of Addiction.)
Published: 2019
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29. Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.

Author: Møllehave LT, Linneberg A, Skaaby T, Knudsen N, Ehlers L, Jørgensen T, and Thuesen BH
Abstract: Background: Iodine fortification (IF) may contribute to changes in costs of thyroid disease treatment through changes in disease patterns. From a health economic perspective, assessment of the development in costs of thyroid disease treatment in the population is pertinent., Objectives: To assess the trends in annual medicine and hospital costs of thyroid disease treatment during 1995-2015 in Denmark, i.e., before and after the introduction of mandatory IF in 2000., Methods: Information on treatments for thyroid disease (antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment) was obtained from nationwide registers. Costs were valued at 2015 prices using sales prices for medicines and the Danish Diagnosis-Related Group (DRG) and Danish Ambulatory Grouping System (DAGS) tariffs of surgeries/radioiodine treatments. Results were adjusted for changes in population size and age and sex distribution., Results: The total direct medicine and hospital costs of thyroid disease treatment increased from EUR ∼190,000 per 100,000 persons in 1995 to EUR ∼270,000 per 100,000 persons in 2015. This was mainly due to linearly increased costs of thyroid hormone therapy and increased costs of thyroid surgery since 2008. Costs of antithyroid medication increased slightly and transiently after IF, while costs of radioiodine treatment remained constant. Costs of thyroid hormone therapy and thyroid surgery did not follow the development in the prevalence of hypothyroidism and structural thyroid diseases observed in concurrent studies., Conclusion: The costs of total direct medicine and hospital costs for thyroid disease treatment in Denmark increased from 1995 to 2015. This is possibly due to several factors, e.g., changes in treatment practices, and the direct effect of IF alone remains to be estimated.
Published: 2018
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30. Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma: a Mendelian randomization meta-analysis.

Author: Skaaby T, Taylor AE, Jacobsen RK, Møllehave LT, Friedrich N, Thuesen BH, Shabanzadeh DM, Paternoster L, Völker U, Nauck M, Völzke H, Munafò M, Hansen T, Pedersen O, Jørgensen T, Grarup N, and Linneberg A
Subjects: Adult, Asthma genetics, Female, Folic Acid blood, Genotype, Humans, Immunoglobulin E blood, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide genetics, Rhinitis, Allergic, Seasonal genetics, Vitamin B 12 blood, Asthma blood, Folic Acid genetics, Mendelian Randomization Analysis, Rhinitis, Allergic, Seasonal blood, Vitamin B 12 genetics
Abstract: Background/objectives: Studies of the effect of vitamin B12 and folate on the risk of asthma and hay fever have shown inconsistent results that may be biased by reverse causation and confounding. We used a Mendelian randomization approach to examine a potential causal effect of vitamin B12 and folate on hay fever, asthma, and selected biomarkers of allergy by using 11 vitamin B12-associated single-nucleotide polymorphisms (SNPs) and 2 folate-associated SNPs as unconfounded markers., Subjects/methods: We included 162,736 participants from 9 population-based studies including the UK Biobank. Results were combined in instrumental variable and meta-analyses and effects expressed as odds ratios (ORs) or estimates with 95% confidence interval (CI)., Results: Using genetic proxies for B12 and folate, instrumental variable analyses did not show evidence for associations between serum B12 and hay fever: OR = 1.02 (95% CI: 0.98, 1.05), asthma: OR = 0.99 (95% CI: 0.95, 1.04), allergic sensitization: OR = 1.02 (95% CI: 0.74, 1.40), or change in serum IgE: 10.0% (95% CI: -9.6%, 29.6%) per 100 pg/ml B12. Similarly, there was no evidence for association between serum folate and hay fever: OR = 0.74 (95% CI: 0.45, 1.21), asthma: OR = 0.80 (95% CI: 0.43, 1.49), or allergic sensitization: OR = 1.92 (95% CI: 0.11, 33.45), but there was a statistically significant association with change in serum IgE: 2.0% (95% CI: 0.43%, 3.58%) per 0.1 ng/ml serum folate., Conclusions: Our results did not support the hypothesis that levels of vitamin B12 and folate are causally related to hay fever, asthma, or biomarkers of allergy, but we found evidence of a positive association between serum folate and serum total IgE.
Published: 2018
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31. Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

Author: Skaaby T, Taylor AE, Thuesen BH, Jacobsen RK, Friedrich N, Møllehave LT, Hansen S, Larsen SC, Völker U, Nauck M, Völzke H, Hansen T, Pedersen O, Jørgensen T, Paternoster L, Munafò M, Grarup N, and Linneberg A
Subjects: Adult, Alleles, Asthma epidemiology, Female, Forced Expiratory Volume, Genetic Predisposition to Disease, Genotype, Humans, Immunoglobulin E immunology, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Rhinitis, Allergic, Seasonal epidemiology, Asthma etiology, Asthma physiopathology, Body Mass Index, Respiratory Function Tests, Rhinitis, Allergic, Seasonal etiology, Rhinitis, Allergic, Seasonal physiopathology
Abstract: Background: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC)., Methods: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI)., Results: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m 2 higher BMI., Conclusions: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)
Published: 2018
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32. Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies.

Author: Møllehave LT, Skaaby T, Simonsen KS, Thuesen BH, Mortensen EL, Sandholt CH, Pedersen O, Grarup N, Hansen T, and Linneberg A
Subjects: Adolescent, Adult, Aged, Anxiety blood, Anxiety psychology, Cohort Studies, Denmark, Depressive Disorder blood, Depressive Disorder psychology, Female, Folic Acid blood, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Psychometrics, Surveys and Questionnaires, Vitamin B 12 blood, White People genetics, Young Adult, Anxiety genetics, Depressive Disorder genetics, Folic Acid genetics, Genetic Predisposition to Disease, Vitamin B 12 genetics
Abstract: Background/objectives: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety., Subjects/methods: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety., Results: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety., Conclusion: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.
Published: 2017
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33. Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population.

Author: Jørgensen NR, Møllehave LT, Hansen YBL, Quardon N, Lylloff L, and Linneberg A
Subjects: Adult, Aged, Aging blood, Biomarkers blood, Blood Chemical Analysis methods, Blood Chemical Analysis standards, Blood Specimen Collection methods, Blood Specimen Collection standards, Body Mass Index, Female, Glomerular Filtration Rate physiology, Humans, Life Style, Male, Middle Aged, Reference Values, Reproducibility of Results, Sex Characteristics, Vitamin D analogs & derivatives, Vitamin D blood, Young Adult, Bone Remodeling physiology, Collagen Type I blood, Peptide Fragments blood, Peptides blood, Procollagen blood
Abstract: Bone turnover markers are used for monitoring osteoporosis treatment. Therefore, we evaluated the agreement between different assays for CTX and PINP and established reference intervals in a cohort of 2300 individuals. We found poor agreement between assays and different reference intervals. This highlights the importance of harmonization of the assays., Introduction: Two reference markers for bone turnover have been proposed: CTX bone resorption and P1NP for bone formation. The purpose of the current study was to establish reference intervals for the two markers in a Danish cohort and to determine the agreement on the two platforms., Methods: Fasting sera from 2308 individuals (1250 males and 1058 females, age range 24-76 years) participating in the Health2006 study were analyzed for CTX and P1NP using the automated IDS-iSYS analyzer and the automated Cobas e411 analyzer. Participants in anti-osteoporotic treatment were excluded, while subjects on hormonal contraceptives were included., Results: There was significant disagreement between both the two P1NP assays with a mean difference of -3 μg/L (LoA -19 to 14) (p < 0.001) and the two CTX assays with a mean difference of 13 ng/L (LoA-187 to 214) (p < 0.001). For CTX, there was a systematic bias: at low values, Cobas measured a higher value than iSYS and at higher concentrations, iSYS measured increasingly higher values than Cobas. Based on the results, we propose three reference intervals for each sex: 25-29, 30-39, and 40-80 years for men, and 25-29, >30 (pre-menopausal), and >30 years (post-menopausal) for women., Conclusions: There is significant disagreement between the IDS-iSYS and Roche Cobas assays for both reference markers. Consequently, the reference intervals for an adult, healthy population are different depending on the analysis method used. Therefore, repeated measurements of patient samples used for monitoring of treatment should be done on the same assay. Moreover, assay-specific reference intervals should be used. Harmonization of assays for BTM is highly warranted.
Published: 2017
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34. Multi-frequency bioelectrical impedance analysis (BIA) compared to magnetic resonance imaging (MRI) for estimation of fat-free mass in colorectal cancer patients treated with chemotherapy.

Author: Palle SS, Møllehave LT, Taheri-Kadkhoda Z, Johansen S, Larsen L, Hansen JW, Jensen NKG, Elingaard AO, Møller AH, Larsen K, and Andersen JR
Subjects: Aged, Body Mass Index, Colonic Neoplasms drug therapy, Colorectal Neoplasms drug therapy, Drug Therapy, Female, Humans, Male, Muscle, Skeletal anatomy & histology, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Skinfold Thickness, Body Composition physiology, Colonic Neoplasms diagnosis, Colorectal Neoplasms diagnosis, Electric Impedance, Magnetic Resonance Imaging methods
Abstract: Background: Changes in body composition in cancer patients during chemotherapy are associated with treatment related toxicities or mortalities. Thus, it is relevant to identify accessible, relatively inexpensive, portable and reliable tools for evaluation of body composition in cancer patients during the course of their treatments., Objective: To examine relationships between single cross-sectional thighs magnetic resonance imaging (MRI), skeletal muscle mass (SM) as reference and multi-frequency bioelectrical impedance analysis (BIA) fat free mass (FFM) in patients with colorectal cancer undergoing chemotherapy., Design: In an observational, prospective study we examine the relationships between single cross-sectional thighs MRI (T1-weighted (1.5 T) SM compared to FFM BIA (8-electrodes multi-frequency Tanita MC780MA)) and FFM skin-fold thickness (ST) (4-points (Harpenden, Skinfold Caliper)) and SM equation for non-obese persons from Lee et al. 2000 (L2000) (based on age, height, weight, sex and race). FFM and SM (kg) were calculated based on either area (MRI) or weight., Results: 18 CRC patients (10 males and 8 females) with mean (SD) age 67 yr (6) were measured at baseline, and 13 were available for follow-up. BIA overestimated FFM kg for all 31 measurements with mean (SD) 18.0 kg (6.0) compared to the MRI. ST overestimated FFM kg with mean 12.4 kg (6.2) and L2000 underestimated SM kg in 18 measurements and overestimated in 13 with a total mean of -4.3 kg (6.8)., Conclusions: BIA and ST were the best alternatives to MRI as they showed constant and thereby correctable errors. The equation, L2000, carried the smallest average measurement error but it was non-constant., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)
Published: 2016
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34 results on '"Møllehave LT"'

1. Trends in treatments of thyroid disease following iodine fortification in Denmark: a nationwide register-based study

2. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

3. Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

4. Rising rural body-mass index is the main driver of the global obesity epidemic in adults

5. Investigating the associations between uncarboxylated matrix gla protein as a proxy for vitamin K status and cardiovascular disease risk factors in a general adult population.

6. Maternal thyroid function in early pregnancy and offspring school performance and neurodevelopmental disorders.

7. Does iodine fortification affect the risk of atrial fibrillation in incident hyperthyroidism? A national register-based cohort.

8. Cohort Profile Update: The Glostrup Population Studies 1964-2024.

9. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

10. Author Correction: The power of genetic diversity in genome-wide association studies of lipids.

11. Z-scores of bone turnover markers calculated from new established sex- and age-specific reference curves are associated to future change in BMD in children and adolescents.

12. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

13. Association between infections and functional somatic disorders: a cross-sectional population-based cohort study.

14. Population-based epidemiology: The Glostrup Population Studies 1964-2021.

15. Socioeconomic influence on treatment with liothyronine and desiccated thyroid extract in Denmark.

16. A saturated map of common genetic variants associated with human height.

17. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

18. Risk-Benefit Assessment of an Increase in the Iodine Fortification Level of Foods in Denmark-A Pilot Study.

19. Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting.

20. Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

21. The power of genetic diversity in genome-wide association studies of lipids.

22. Influence of educational level on test and treatment for incident hypothyroidism.

23. Reference intervals in Danish children and adolescents for bone turnover markers carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP).

24. Symptoms and biomarkers associated with undiagnosed celiac seropositivity.

25. Uncarboxylated matrix Gla-protein: A biomarker of vitamin K status and cardiovascular risk.

26. The association of thyroid stimulation hormone levels with incident ischemic heart disease, incident stroke, and all-cause mortality.

27. Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase-reference intervals and confounders for two bone formation markers.

28. Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

29. Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.

30. Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma: a Mendelian randomization meta-analysis.

31. Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

32. Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies.

33. Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population.

34. Multi-frequency bioelectrical impedance analysis (BIA) compared to magnetic resonance imaging (MRI) for estimation of fat-free mass in colorectal cancer patients treated with chemotherapy.

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34 results on '"Møllehave LT"'

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