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Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Abstract: 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.

 Autoría: Reppe S., Wang Y., Thompson W.K., McEvoy L.K., Schork A.J., Zuber V., LeBlanc M., Bettella F., Mills I.G., Desikan R.S., Djurovic S., Gautvik K.M., Dale A.M., Andreassen O.A., Estrada K., Styrkarsdottir U., Evangelou E., Hsu Y.H., Duncan E.L., Ntzani E.E., Oei L., Albagha O.M.E., Amin N., Kemp J.P., Koller D.L., Li G., Liu C.T., Minster R.L., Moayyeri A., Vandenput L., Willner D., Xiao S.M., Yerges-Armstrong L.M., Zheng H.F., Al

 Fuente: PLoS One, 2015, 10(12), e0144531

 Año de publicación: 2015

 Nº de páginas: 20

 Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0144531

 ISSN: 1932-6203

 Url de la publicación: https://doi.org/10.1371/journal.pone.0144531

Autoría

REPPE, SJUR

WANG, YUNPENG

THOMPSON, WESLEY K.

MCEVOY, LINDA K.

SCHORK, ANDREW J.

ZUBER, VERENA

LEBLANC, MARISSA

BETTELLA, FRANCESCO

MILLS, IAN G.

DESIKAN, RAHUL S.

DJUROVIC, SRDJAN

GAUTVIK, KAARE M.

DALE, ANDERS M.

ANDREASSEN, OLE A.

MARIA TERESA ZARRABEITIA CIMIANO