title: A Mendelian Randomization Study of the Effect of Type-2 Diabetes and Glycemic Traits on Bone Mineral Density.
abstract: Type-2 diabetes (T2D) is associated in observational studies with both higher bone mineral density (BMD) and higher fracture risk for given BMD. These relationships may however be confounded by factors such as body mass index (BMI). Here we used Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on BMD. We identified genetic variants strongly associated with T2D risk (34,840 T2D cases and 114,981 controls) and fasting glucose (133,010 nondiabetic individuals), but not associated with BMI, and determined the effects of these variants on BMD (up to 83,894 individuals). Using these variants as instrumental variables, we found that a genetically-increased risk of T2D increased femoral neck BMD (+0.034 SD in BMD per unit increase in log-odds of T2D [95% CI, 0.001 to 0.067; p = 0.044]). Genetically-increased fasting glucose also increased femoral neck BMD (+0.13 SD in BMD per mmol/L increase in fasting glucose [95% CI, 0.01 to 0.25; p = 0.034]). Similar nonsignificant trends were observed for the effects of T2D and fasting glucose on lumbar spine BMD. Our results indicate that both genetically-increased T2D risk and genetically-increased fasting glucose have weak positive effects on BMD. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.|Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Ahmad
authors.affiliation: Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Leong
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: John A
authors.initials: JA
authors.lastname: Morris
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Forgetta
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.|Division of Endocrinology and Metabolism, Department of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mujammami
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.|Department of Medicine, McGill University, Montreal, Quebec, Canada.|Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
mesh_terms: D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D015519:Bone Density / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005272:Femur Neck / Q000378:metabolism*; D055106:Genome-Wide Association Study; D038321:Glycemic Index; D006801:Humans; D008297:Male; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D001786:Blood Glucose
keywords: BONE MINERAL DENSITY; DIABETES; HUMAN ASSOCIATION STUDES; OSTEOPOROSIS