Genome-wide association study of circulating interleukin 6 levels identifies novel loci


Por: Ahluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppala, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, JJ, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellstrom, D, Mooijaart, SP, Muller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Raikkonen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, St Pourcain, B, Timpson, NJ, Trollor, J, van Dongen, J, Van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Volker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, YPC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, Jukema, JW, Koenig, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimaki, T, Marz, W, Mather, KA, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sorensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, Wannamethee, SG, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, Alizadeh, BZ, CHARGE Inflammation Working Grp

Publicada: 1 mar 2021 Ahead of Print: 1 ene 2021
Resumen:
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Filiaciones:
Ahluwalia, TS:
 Steno Diabet Ctr Copenhagen, DK-2820 Gentofte, Denmark

 Univ Copenhagen, Bioinformat Ctr, Dept Biol, DK-2200 Copenhagen, Denmark

Prins, BP:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

Abdollahi, M:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

Armstrong, NJ:
 Murdoch Univ, Math & Stat, Perth, WA 6150, Australia

Aslibekyan, S:
 Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA

Bain, L:
 QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia

Jefferis, B:
 UCL, UCL Inst Epidemiol & Hlth Care, Dept Primary Care & Populat Hlth, London NW3 2PF, England

Baumert, J:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

Beekman, M:
 Leiden Univ Med Ctr, Dept Biomed Data Sci, Sect Mol Epidemiol, NL-2300 RC Leiden, Netherlands

Ben-Shlomo, Y:
 Univ Bristol, Populat Hlth Sci, Bristol BS8 2PS, Avon, England

Bis, JC:
 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

Mitchell, BD:
 Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21202 USA

de Geus, E:
 Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands

 Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, NL-1105 AZ Amsterdam, Netherlands

Delgado, GE:
 Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, D-68167 Mannheim, Germany

Marek, D:
 SIB Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

Eriksson, J:
 Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res CBAR, Dept Internal Med & Clin Nutr, S-41345 Gothenburg, Sweden

 Univ Helsinki, Natl Inst Hlth & Welf, Helsinki 00014, Finland

 Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland

Kajantie, E:
 Natl Inst Hlth & Welf, Chron Dis Prevent Unit, POB 30, Helsinki 00271, Finland

 Helsinki Univ Cent Hosp, Hosp Children & Adolescents, Helsinki 00014, Finland

 Univ Helsinki, Helsinki 00014, Finland

Kanoni, S:
 Queen Mary Univ London, Barts & London Med Sch, William Harvey Res Inst, London EC1M 6BQ, England

Kemp, JP:
 Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia

 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

Lu, C:
 Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA

Marioni, RE:
 Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

 Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

McLachlan, S:
 Univ Edinburgh, Usher Inst, Edinburgh EH8 9AG, Midlothian, Scotland

Milaneschi, Y:
 Vrije Univ, Dept Psychiat, Amsterdam UMC, NL-1081 HJ Amsterdam, Netherlands

Nolte, IM:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

Petrelis, AM:
 Univ Lorraine, IGE PCV, INSERM, F-54000 Nancy, France

Porcu, E:
 CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, CA, Italy

Sabater-Lleal, M:
 Karolinska Inst, Ctr Mol Med, Dept Med Solna, Cardiovasc Med, S-17176 Stockholm, Sweden

 Inst Invest Biomed St Pau IIB St Pau, Unit Genom Complex Dis, Barcelona 08041, Spain

Naderi, E:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

Seppala, I:
 Tampere Univ, Fac Med & Hlth Technol, Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland

 Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Tampere 33520, Finland

Shah, T:
 UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

Singhal, G:
 Univ Adelaide, Adelaide Med Sch, Discipline Psychiat, Adelaide, SA 5005, Australia

Standl, M:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

Teumer, A:
 Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany

Thalamuthu, A:
 Univ New South Wales, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW 2052, Australia

Thiering, E:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

 Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutr Med, D-80337 Munich, Germany

Trompet, S:
 Leiden Univ Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands

 Leiden Univ Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands

Ballantyne, CM:
 Baylor Coll Med, Houston, TX 77030 USA

Benjamin, EJ:
 Natl Heart Lung & Blood Inst, Framingham, MA 01702 USA

 Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA

 Boston Univ, Dept Med, Sect Cardiovasc Med & Prevent Med, Sch Med, Boston, MA 02118 USA

Casas, JP:
 VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA 02130 USA

Toben, C:
 Univ Adelaide, Adelaide Med Sch, Discipline Psychiat, Adelaide, SA 5005, Australia

Dedoussis, G:
 Harokopio Univ, Dept Nutr Dietet, Athens 17671, Greece

Deelen, J:
 Leiden Univ Med Ctr, Dept Biomed Data Sci, Sect Mol Epidemiol, NL-2300 RC Leiden, Netherlands

 Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

Durda, P:
 Univ Vermont, Larner Coll Med, Dept Pathol & Lab Med, Burlington, VT 05405 USA

Engmann, J:
 UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

Feitosa, MF:
 Washington Univ, Dept Genet, Div Stat Genom, Sch Med, St Louis, MO 63110 USA

Grallert, H:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

 German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

Hammarstedt, A:
 Univ Gothenburg, Dept Mol & Clin Med, Lundberg Lab Diabet Res, Sahlgrenska Acad, SE-41345 Gothenburg, Sweden

Harris, SE:
 Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

 Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

Homuth, G:
 Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany

Hottenga, JJ:
 Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands

 Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, NL-1105 AZ Amsterdam, Netherlands

Jalkanen, S:
 Univ Turku, MediCity Res Lab, Turku 20520, Finland

 Univ Turku, Dept Med Microbiol & Immunol, Turku 20520, Finland

Jamshidi, Y:
 St Georges Univ London, Mol & Clin Sci Inst, Genet Res Ctr, London SW17 0RE, England

Jawahar, MC:
 Univ Adelaide, Adelaide Med Sch, Discipline Psychiat, Adelaide, SA 5005, Australia

Jess, T:
 Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

Kivimaki, M:
 UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London WC1E 7HB, England

Kleber, ME:
 Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, D-68167 Mannheim, Germany

Lahti, J:
 Univ Turku, Turku Inst Adv Studies, Turku 20014, Finland

 Univ Helsinki, Dept Psychol & Logoped, Helsinki 00014, Finland

Liu, Y:
 Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA

Marques-Vidal, P:
 Lausanne Univ Hosp CHUV, Dept Internal Med, CH-1011 Lausanne, Switzerland

 Univ Lausanne, CH-1011 Lausanne, Switzerland

Mellstrom, D:
 Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res CBAR, Dept Internal Med & Clin Nutr, S-41345 Gothenburg, Sweden

Mooijaart, SP:
 Leiden Univ Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands

Muller-Nurasyid, M:
 Ludwig Maximilians Univ LMU Munich, Fac Med, IBE, D-81377 Munich, Germany

 Johhanes Gutenberg Univ, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat IMBEI, D-55101 Mainz, Germany

Penninx, B:
 Vrije Univ, Dept Psychiat, Amsterdam UMC, NL-1081 HJ Amsterdam, Netherlands

Revez, JA:
 QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia

Rossing, P:
 Steno Diabet Ctr Copenhagen, DK-2820 Gentofte, Denmark

 Univ Copenhagen, Dept Clin Med, DK-2200 Copenhagen, Denmark

Raikkonen, K:
 Univ Helsinki, Dept Psychol & Logoped, Helsinki 00014, Finland

Sattar, N:
 BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow G12 8TA, Lanark, Scotland

Scharnagl, H:
 Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria

Sennblad, B:
 Karolinska Inst, Ctr Mol Med, Dept Med Solna, Cardiovasc Med, S-17176 Stockholm, Sweden

 Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, S-75124 Uppsala, Sweden

Silveira, A:
 Karolinska Inst, Ctr Mol Med, Dept Med Solna, Cardiovasc Med, S-17176 Stockholm, Sweden

St Pourcain, B:
 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

 Max Planck Inst Psycholinguist, NL-6525 XD Nijmegen, Netherlands

 Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 AJ Nijmegen, Netherlands

Timpson, NJ:
 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

Trollor, J:
 Univ New South Wales, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW 2052, Australia

 Univ New South Wales, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Sydney, NSW 2031, Australia

van Dongen, J:
 Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands

 Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, NL-1105 AZ Amsterdam, Netherlands

Van Heemst, D:
 Baylor Coll Med, Houston, TX 77030 USA

Visvikis-Siest, S:
 Univ Lorraine, IGE PCV, INSERM, F-54000 Nancy, France

Vollenweider, P:
 Lausanne Univ Hosp CHUV, Dept Internal Med, CH-1011 Lausanne, Switzerland

 Univ Lausanne, CH-1011 Lausanne, Switzerland

Volker, U:
 Univ Turku, MediCity Res Lab, Turku 20520, Finland

Waldenberger, M:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

Willemsen, G:
 Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands

 Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, NL-1105 AZ Amsterdam, Netherlands

Zabaneh, D:
 UCL, Dept Genet, Genet Inst, London WC1E 6BT, England

Morris, RW:
 Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol BS8 1UD, Avon, England

Arnett, DK:
 Univ Kentucky, Coll Publ Hlth, Deans Off, Lexington, KY 40536 USA

Baune, BT:
 Univ Melbourne, Melbourne Med Sch, Dept Psychiat, Parkville, Vic 3000, Australia

 Univ Munster, Dept Psychiat & Psychotherapy, D-48149 Munster, Germany

 Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3000, Australia

Boomsma, DI:
 Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands

 Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, NL-1105 AZ Amsterdam, Netherlands

Chang, YPC:
 Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21202 USA

Deary, IJ:
 Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

 Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

Deloukas, P:
 Queen Mary Univ London, Barts & London Med Sch, William Harvey Res Inst, London EC1M 6BQ, England

 Queen Mary Univ London, Ctr Genom Hlth, London EC1M 6BQ, England

Eriksson, JG:
 Univ Helsinki, Natl Inst Hlth & Welf, Helsinki 00014, Finland

 Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland

Evans, DM:
 Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia

 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

Ferreira, MA:
 QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia

Gaunt, T:
 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS6 2BN, Avon, England

 Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 2BN, Avon, England

Gudnason, V:
 Iceland Heart Assoc, IS-201 Kopavogur, Iceland

 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

Hamsten, A:
 Karolinska Inst, Ctr Mol Med, Dept Med Solna, Cardiovasc Med, S-17176 Stockholm, Sweden

Heinrich, J:
 Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

 Ludwig Maximilians Univ Munchen, Inst & Clin Occupat Social & Environm Med, Univ Hosp, D-81377 Munich, Germany

 Univ Melbourne, Melbourne Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic 3010, Australia

Hingorani, A:
 UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

Humphries, SE:
 UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

Jukema, JW:
 Leiden Univ Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands

 Durrer Ctr Cardiogenet Res, NL-1105 AZ Amsterdam, Netherlands

Koenig, W:
 Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany

 DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80336 Munich, Germany

 Univ Ulm, Inst Epidemiol & Med Biometry, D-89081 Ulm, Germany

Kumari, M:
 UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London WC1E 7HB, England

 Univ Essex, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England

Kutalik, Z:
 SIB Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

 Univ Lausanne, Univ Ctr Primary Care & Publ Hlth, CH-1010 Lausanne, Switzerland

Lawlor, DA:
 Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS6 2BN, Avon, England

 Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 2BN, Avon, England

Lehtimaki, T:
 Tampere Univ, Fac Med & Hlth Technol, Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland

 Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Tampere 33520, Finland

Marz, W:
 Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, D-68167 Mannheim, Germany

 Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria

 SYNALB Holding Deutschland GmbH, SYNLAB Acad, D-68163 Mannheim, Germany

Mather, KA:
 Univ New South Wales, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW 2052, Australia

 Neurosci Res Australia, Sydney, NSW 2031, Australia

Naitza, S:
 CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, CA, Italy

Nauck, M:
 Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany

 DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany

Ohlsson, C:
 Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res CBAR, Dept Internal Med & Clin Nutr, S-41345 Gothenburg, Sweden

Price, JF:
 Univ Edinburgh, Usher Inst, Edinburgh EH8 9AG, Midlothian, Scotland

Raitakari, O:
 Univ Turku, Turku Univ Hosp, Ctr Populat Hlth Res, Turku 20520, Finland

 Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland

 Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20014, Finland

Rice, K:
 Univ Washington, Dept Biostat, Seattle, WA 98195 USA

Sachdev, PS:
 Univ New South Wales, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW 2052, Australia

 Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW 2031, Australia

Slagboom, E:
 Leiden Univ Med Ctr, Dept Biomed Data Sci, Sect Mol Epidemiol, NL-2300 RC Leiden, Netherlands

 Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

Sorensen, TIA:
 Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Sect Metab Genet, DK-2200 Copenhagen, Denmark

 Univ Copenhagen, Dept Publ Hlth, Sect Epidemiol, DK-1014 Copenhagen, Denmark

Spector, T:
 Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

Stacey, D:
 Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England

Stathopoulou, MG:
 Univ Lorraine, IGE PCV, INSERM, F-54000 Nancy, France

Tanaka, T:
 NIA, Translat Gerontol Branch, Longitudinal Study Sect, Baltimore, MD 21224 USA

Wannamethee, SG:
 UCL, UCL Inst Epidemiol & Hlth Care, Dept Primary Care & Populat Hlth, London NW3 2PF, England

Whincup, P:
 St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England

Rotter, JI:
 Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Lundquist Inst, Torrance, CA 90502 USA

Dehghan, A:
 Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

Boerwinkle, E:
 Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA

 Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

Psaty, BM:
 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

 Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA

 Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA

Snieder, H:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

Alizadeh, BZ:
 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands
ISSN: 09646906
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 30 Número: 5
Páginas: 393-409
WOS Id: 000654638100007
ID de PubMed: 33517400
imagen Green Published, Green Accepted, hybrid

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