Line Rode1, Børge G Nordestgaard, Maren Weischer, Stig E Bojesen. 1. Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark; and Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Abstract
CONTEXT: Obesity is associated with short telomere length. The cause of this association is unknown. OBJECTIVE: We hypothesized that genetically increased body mass index (BMI) is associated with telomere length shortening and that low-grade inflammation might contribute through elevated C-reactive protein. SETTING AND DESIGN: We studied 45,069 individuals from the Copenhagen General Population Study with measurements of leukocyte telomere length, BMI, and C-reactive protein in a Mendelian randomization study. Using the three obesity-associated polymorphisms FTO rs9939609, MC4R rs17782313, and TMEM18 rs6548238, and the CRP promoter polymorphism rs3091244 in instrumental variable analyses, we estimated the associations between genetically increased BMI and telomere length and between genetically increased C-reactive protein and telomere length. RESULTS: In multivariable-adjusted observational analyses, telomere length decreased with seven base pairs (95% confidence interval, -9--5) per unit increase in BMI, and further adjustment for C-reactive protein attenuated this association to -5 base pairs (-8--3). In accordance, instrumental variable analysis showed a non-significant telomere length shortening of six base pairs (-37-25) per unit increase in genetically determined BMI. Furthermore, in observational analyses, telomere length decreased with nine base pairs (-16--2) for a doubling in C-reactive protein, supported by the instrumental variable analyses showing a corresponding genetically determined decrease of 66 base pairs (-124--7). CONCLUSIONS: High BMI is associated with short telomere length observationally. This might possibly be mediated through elevated C-reactive protein, given that genetically elevated C-reactive protein levels are associated with short telomere length.
CONTEXT: Obesity is associated with short telomere length. The cause of this association is unknown. OBJECTIVE: We hypothesized that genetically increased body mass index (BMI) is associated with telomere length shortening and that low-grade inflammation might contribute through elevated C-reactive protein. SETTING AND DESIGN: We studied 45,069 individuals from the Copenhagen General Population Study with measurements of leukocyte telomere length, BMI, and C-reactive protein in a Mendelian randomization study. Using the three obesity-associated polymorphisms FTO rs9939609, MC4Rrs17782313, and TMEM18rs6548238, and the CRP promoter polymorphism rs3091244 in instrumental variable analyses, we estimated the associations between genetically increased BMI and telomere length and between genetically increased C-reactive protein and telomere length. RESULTS: In multivariable-adjusted observational analyses, telomere length decreased with seven base pairs (95% confidence interval, -9--5) per unit increase in BMI, and further adjustment for C-reactive protein attenuated this association to -5 base pairs (-8--3). In accordance, instrumental variable analysis showed a non-significant telomere length shortening of six base pairs (-37-25) per unit increase in genetically determined BMI. Furthermore, in observational analyses, telomere length decreased with nine base pairs (-16--2) for a doubling in C-reactive protein, supported by the instrumental variable analyses showing a corresponding genetically determined decrease of 66 base pairs (-124--7). CONCLUSIONS: High BMI is associated with short telomere length observationally. This might possibly be mediated through elevated C-reactive protein, given that genetically elevated C-reactive protein levels are associated with short telomere length.
Authors: Marij Gielen; Geja J Hageman; Evangelia E Antoniou; Katarina Nordfjall; Massimo Mangino; Muthuswamy Balasubramanyam; Tim de Meyer; Audrey E Hendricks; Erik J Giltay; Steven C Hunt; Jennifer A Nettleton; Klelia D Salpea; Vanessa A Diaz; Ramin Farzaneh-Far; Gil Atzmon; Sarah E Harris; Lifang Hou; David Gilley; Iiris Hovatta; Jeremy D Kark; Hisham Nassar; David J Kurz; Karen A Mather; Peter Willeit; Yun-Ling Zheng; Sofia Pavanello; Ellen W Demerath; Line Rode; Daniel Bunout; Andrew Steptoe; Lisa Boardman; Amelia Marti; Belinda Needham; Wei Zheng; Rosalind Ramsey-Goldman; Andrew J Pellatt; Jaakko Kaprio; Jonathan N Hofmann; Christian Gieger; Giuseppe Paolisso; Jacob B H Hjelmborg; Lisa Mirabello; Teresa Seeman; Jason Wong; Pim van der Harst; Linda Broer; Florian Kronenberg; Barbara Kollerits; Timo Strandberg; Dan T A Eisenberg; Catherine Duggan; Josine E Verhoeven; Roxanne Schaakxs; Raffaela Zannolli; Rosana M R Dos Reis; Fadi J Charchar; Maciej Tomaszewski; Ute Mons; Ilja Demuth; Andrea Elena Iglesias Molli; Guo Cheng; Dmytro Krasnienkov; Bianca D'Antono; Marek Kasielski; Barry J McDonnell; Richard Paul Ebstein; Kristina Sundquist; Guillaume Pare; Michael Chong; Maurice P Zeegers Journal: Am J Clin Nutr Date: 2018-09-01 Impact factor: 7.045
Authors: Ashley E Mason; Frederick M Hecht; Jennifer J Daubenmier; David A Sbarra; Jue Lin; Patricia J Moran; Samantha G Schleicher; Michael Acree; Aric A Prather; Elissa S Epel Journal: Psychosom Med Date: 2018-09 Impact factor: 4.312
Authors: M Laimer; A Melmer; C Lamina; J Raschenberger; P Adamovski; J Engl; C Ress; A Tschoner; C Gelsinger; L Mair; S Kiechl; J Willeit; P Willeit; C Stettler; H Tilg; F Kronenberg; C Ebenbichler Journal: Int J Obes (Lond) Date: 2015-11-26 Impact factor: 5.095
Authors: Julia B Greer; Phil Greer; Bimaljit S Sandhu; Samer Alkaade; C Mel Wilcox; Michelle A Anderson; Stuart Sherman; Timothy B Gardner; Michele D Lewis; Nalini M Guda; Thiruvengadam Muniraj; Darwin Conwell; Gregory A Cote; Christopher E Forsmark; Peter A Banks; Gong Tang; Kim Stello; Andres Gelrud; Randall E Brand; Adam Slivka; David C Whitcomb; Dhiraj Yadav Journal: Nutr Clin Pract Date: 2018-08-13 Impact factor: 3.080