UNLABELLED: Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate this relationship, the present study aims to investigate the relative influence of genetic and environmental factors on four key cytokines involved in the human immune response (Interleukin (IL)-1β, IL-6, IL-10 and Tumor Necrosis Factor (TNF)-α). In addition, the role of age as a possible moderator on these influences was evaluated. METHODS: The study was conducted in 1603 females from the Twins UK registry, with mean age ± SD of 60.4 ± 12.2 years, including 863 monozygotic twins (385 pairs and 93 singletons) and 740 dizygotic twins (321 pairs and 98 singletons). Heritability was estimated using structural equation modeling. The role of age as a moderator was evaluated using gene-age interaction models. RESULTS: Heritabilities were moderate for IL-1β (range: 0.27-0.32) and IL-10 (0.30) and low for IL-6 (range: 0.15-0.16) and TNF-α (range: 0.17-0.23). For IL-1β, heritability declines with age due to an increase in unique environmental factors. For TNF-α, heritability increases with age due to a decrease in unique environmental factors. CONCLUSION: The current findings illustrate the importance of genetic and environmental influences on four cytokines involved in the human immune response. For two of these there is evidence that heritability changes with age owing to changes in environmental factors unique to the individual.
UNLABELLED: Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate this relationship, the present study aims to investigate the relative influence of genetic and environmental factors on four key cytokines involved in the human immune response (Interleukin (IL)-1β, IL-6, IL-10 and Tumor Necrosis Factor (TNF)-α). In addition, the role of age as a possible moderator on these influences was evaluated. METHODS: The study was conducted in 1603 females from the Twins UK registry, with mean age ± SD of 60.4 ± 12.2 years, including 863 monozygotic twins (385 pairs and 93 singletons) and 740 dizygotic twins (321 pairs and 98 singletons). Heritability was estimated using structural equation modeling. The role of age as a moderator was evaluated using gene-age interaction models. RESULTS: Heritabilities were moderate for IL-1β (range: 0.27-0.32) and IL-10 (0.30) and low for IL-6 (range: 0.15-0.16) and TNF-α (range: 0.17-0.23). For IL-1β, heritability declines with age due to an increase in unique environmental factors. For TNF-α, heritability increases with age due to a decrease in unique environmental factors. CONCLUSION: The current findings illustrate the importance of genetic and environmental influences on four cytokines involved in the human immune response. For two of these there is evidence that heritability changes with age owing to changes in environmental factors unique to the individual.
Authors: Tarunveer S Ahluwalia; Bram P Prins; Mohammadreza Abdollahi; Nicola J Armstrong; Stella Aslibekyan; Lisa Bain; Barbara Jefferis; Jens Baumert; Marian Beekman; Yoav Ben-Shlomo; Joshua C Bis; Braxton D Mitchell; Eco de Geus; Graciela E Delgado; Diana Marek; Joel Eriksson; Eero Kajantie; Stavroula Kanoni; John P Kemp; Chen Lu; Riccardo E Marioni; Stela McLachlan; Yuri Milaneschi; Ilja M Nolte; Alexandros M Petrelis; Eleonora Porcu; Maria Sabater-Lleal; Elnaz Naderi; Ilkka Seppälä; Tina Shah; Gaurav Singhal; Marie Standl; Alexander Teumer; Anbupalam Thalamuthu; Elisabeth Thiering; Stella Trompet; Christie M Ballantyne; Emelia J Benjamin; Juan P Casas; Catherine Toben; George Dedoussis; Joris Deelen; Peter Durda; Jorgen Engmann; Mary F Feitosa; Harald Grallert; Ann Hammarstedt; Sarah E Harris; Georg Homuth; Jouke-Jan Hottenga; Sirpa Jalkanen; Yalda Jamshidi; Magdalene C Jawahar; Tine Jess; Mika Kivimaki; Marcus E Kleber; Jari Lahti; Yongmei Liu; Pedro Marques-Vidal; Dan Mellström; Simon P Mooijaart; Martina Müller-Nurasyid; Brenda Penninx; Joana A Revez; Peter Rossing; Katri Räikkönen; Naveed Sattar; Hubert Scharnagl; Bengt Sennblad; Angela Silveira; Beate St Pourcain; Nicholas J Timpson; Julian Trollor; Jenny van Dongen; Diana Van Heemst; Sophie Visvikis-Siest; Peter Vollenweider; Uwe Völker; Melanie Waldenberger; Gonneke Willemsen; Delilah Zabaneh; Richard W Morris; Donna K Arnett; Bernhard T Baune; Dorret I Boomsma; Yen-Pei C Chang; Ian J Deary; Panos Deloukas; Johan G Eriksson; David M Evans; Manuel A Ferreira; Tom Gaunt; Vilmundur Gudnason; Anders Hamsten; Joachim Heinrich; Aroon Hingorani; Steve E Humphries; J Wouter Jukema; Wolfgang Koenig; Meena Kumari; Zoltan Kutalik; Deborah A Lawlor; Terho Lehtimäki; Winfried März; Karen A Mather; Silvia Naitza; Matthias Nauck; Claes Ohlsson; Jackie F Price; Olli Raitakari; Ken Rice; Perminder S Sachdev; Eline Slagboom; Thorkild I A Sørensen; Tim Spector; David Stacey; Maria G Stathopoulou; Toshiko Tanaka; S Goya Wannamethee; Peter Whincup; Jerome I Rotter; Abbas Dehghan; Eric Boerwinkle; Bruce M Psaty; Harold Snieder; Behrooz Z Alizadeh Journal: Hum Mol Genet Date: 2021-04-27 Impact factor: 6.150
Authors: Amanda L Rodrigue; Emma Em Knowles; Josephine Mollon; Samuel R Mathias; Marinka Mg Koenis; Juan M Peralta; Ana C Leandro; Peter T Fox; Emma Sprooten; Peter Kochunov; Rene L Olvera; Ravindranath Duggirala; Laura Almasy; Joanne E Curran; John Blangero; David C Glahn Journal: Hum Brain Mapp Date: 2019-06-11 Impact factor: 5.399
Authors: Stella Aslibekyan; Golareh Agha; Elena Colicino; Anh N Do; Jari Lahti; Symen Ligthart; Riccardo E Marioni; Carola Marzi; Michael M Mendelson; Toshiko Tanaka; Matthias Wielscher; Devin M Absher; Luigi Ferrucci; Oscar H Franco; Christian Gieger; Harald Grallert; Dena Hernandez; Tianxiao Huan; Stella Iurato; Roby Joehanes; Allan C Just; Sonja Kunze; Honghuang Lin; Chunyu Liu; James B Meigs; Joyce B J van Meurs; Ann Zenobia Moore; Annette Peters; Holger Prokisch; Katri Räikkönen; Wolfgang Rathmann; Michael Roden; Katharina Schramm; Joel D Schwartz; John M Starr; André G Uitterlinden; Pantel Vokonas; Melanie Waldenberger; Chen Yao; Degui Zhi; Andrea A Baccarelli; Stefania Bandinelli; Ian J Deary; Abbas Dehghan; Johan Eriksson; Christian Herder; Marjo-Riitta Jarvelin; Daniel Levy; Donna K Arnett Journal: JAMA Cardiol Date: 2018-06-01 Impact factor: 14.676