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

GEFOS Consortium

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0144531
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

Fingerprint

bone density
Medical problems
Bone Density
cardiovascular diseases
Minerals
diabetes
Bone
Cardiovascular Diseases
risk factors
loci
Blood Pressure
Blood pressure
Type 2 Diabetes Mellitus
single nucleotide polymorphism
Single Nucleotide Polymorphism
Polymorphism
Comorbidity
Genetic Pleiotropy
Nucleotides
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci. / GEFOS Consortium.

In: PLoS One, Vol. 10, No. 12, e0144531, 01.12.2015.

Research output: Contribution to journalArticle

@article{c1a838d20e154368a3fd85b735f8e51c,
title = "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.",
author = "{GEFOS Consortium} and Sjur Reppe and Yunpeng Wang and Thompson, {Wesley K.} and McEvoy, {Linda K.} and Schork, {Andrew J.} and Verena Zuber and Marissa LeBlanc and Francesco Bettella and Mills, {Ian G.} and Desikan, {Rahul S.} and Srdjan Djurovic and Gautvik, {Kaare M.} and Dale, {Anders M.} and Andreassen, {Ole A.} and Karol Estrada and Unnur Styrkarsdottir and Evangelos Evangelou and Hsu, {Yi Hsiang} and Duncan, {Emma L.} and Ntzani, {Evangelia E.} and Ling Oei and Albagha, {Omar M E} and Najaf Amin and Kemp, {John P.} and Koller, {Daniel L.} and Guo Li and Liu, {Ching Ti} and Minster, {Ryan L.} and Alireza Moayyeri and Liesbeth Vandenput and Dana Willner and Xiao, {Su Mei} and Yerges-Armstrong, {Laura M.} and Zheng, {Hou Feng} and Nerea Alonso and Joel Eriksson and Kammerer, {Candace M.} and Kaptoge, {Stephen K.} and Leo, {Paul J.} and Gudmar Thorleifsson and Wilson, {Scott G.} and Wilson, {James F.} and Ville Aalto and Markku Alen and Aragaki, {Aaron K.} and Thor Aspelund and Center, {Jacqueline R.} and Zoe Dailiana and Duggan, {David J.} and Robbins, {John A}",
year = "2015",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0144531",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

AU - GEFOS Consortium

AU - Reppe, Sjur

AU - Wang, Yunpeng

AU - Thompson, Wesley K.

AU - McEvoy, Linda K.

AU - Schork, Andrew J.

AU - Zuber, Verena

AU - LeBlanc, Marissa

AU - Bettella, Francesco

AU - Mills, Ian G.

AU - Desikan, Rahul S.

AU - Djurovic, Srdjan

AU - Gautvik, Kaare M.

AU - Dale, Anders M.

AU - Andreassen, Ole A.

AU - Estrada, Karol

AU - Styrkarsdottir, Unnur

AU - Evangelou, Evangelos

AU - Hsu, Yi Hsiang

AU - Duncan, Emma L.

AU - Ntzani, Evangelia E.

AU - Oei, Ling

AU - Albagha, Omar M E

AU - Amin, Najaf

AU - Kemp, John P.

AU - Koller, Daniel L.

AU - Li, Guo

AU - Liu, Ching Ti

AU - Minster, Ryan L.

AU - Moayyeri, Alireza

AU - Vandenput, Liesbeth

AU - Willner, Dana

AU - Xiao, Su Mei

AU - Yerges-Armstrong, Laura M.

AU - Zheng, Hou Feng

AU - Alonso, Nerea

AU - Eriksson, Joel

AU - Kammerer, Candace M.

AU - Kaptoge, Stephen K.

AU - Leo, Paul J.

AU - Thorleifsson, Gudmar

AU - Wilson, Scott G.

AU - Wilson, James F.

AU - Aalto, Ville

AU - Alen, Markku

AU - Aragaki, Aaron K.

AU - Aspelund, Thor

AU - Center, Jacqueline R.

AU - Dailiana, Zoe

AU - Duggan, David J.

AU - Robbins, John A

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84958012773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958012773&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0144531

DO - 10.1371/journal.pone.0144531

M3 - Article

C2 - 26695485

AN - SCOPUS:84958012773

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0144531

ER -