Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

Original publication

DOI

10.1371/journal.pone.0144531

Type

Journal article

Journal

PloS one

Publication Date

01/2015

Volume

10

Addresses

Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Keywords

GEFOS Consortium, Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Waist-Hip Ratio, Bone Density, Polymorphism, Single Nucleotide, Models, Genetic, Gene Regulatory Networks, Genome-Wide Association Study, Genetic Loci, Genetic Pleiotropy