Cargando…

Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density

BACKGROUND: Genome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together...

Descripción completa

Detalles Bibliográficos
Autores principales: He, Pei, Meng, Xiang-He, Zhang, Xiao, Lin, Xu, Zhang, Qiang, Jiang, Ri-Li, Schiller, Martin R., Deng, Fei-Yan, Deng, Hong-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388689/
https://www.ncbi.nlm.nih.gov/pubmed/32774344
http://dx.doi.org/10.3389/fgene.2020.00772
_version_ 1783564356062019584
author He, Pei
Meng, Xiang-He
Zhang, Xiao
Lin, Xu
Zhang, Qiang
Jiang, Ri-Li
Schiller, Martin R.
Deng, Fei-Yan
Deng, Hong-Wen
author_facet He, Pei
Meng, Xiang-He
Zhang, Xiao
Lin, Xu
Zhang, Qiang
Jiang, Ri-Li
Schiller, Martin R.
Deng, Fei-Yan
Deng, Hong-Wen
author_sort He, Pei
collection PubMed
description BACKGROUND: Genome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the SNPs or putative causal SNPs associated with eBMD were also associated with FNK-BMD. METHODS: Novel loci associated with eBMD and FNK-BMD were identified by the genetic pleiotropic conditional false discovery rate (cFDR) method. Shared putative causal variants between eBMD and FNK-BMD and putative causal SNPs for each trait were identified by the colocalization method. Mendelian randomization analysis addresses the causal relationship between eBMD/FNK-BMD and fracture. RESULTS: We identified 9,500 (cFDR < 9.8E-6), 137 (cFDR < 8.9E-4) and 124 SNPs associated with eBMD, FNK-BMD, and both eBMD and FNK-BMD, respectively, with 37 genomic regions where there was a SNP that influences both eBMD and FNK-BMD. Most genomic regions only contained putative causal SNPs associated with eBMD and 3 regions contained two distinct putative causal SNPs influenced both traits, respectively. We demonstrated a causal effect of FNK-BMD/eBMD on fracture. CONCLUSION: Most of SNPs or putative causal SNPs associated with FNK-BMD were also associated with eBMD. However, most of SNPs or putative causal SNPs associated with eBMD were not associated with FNK-BMD. The novel variants we identified may help to account for the additional proportion of variance of each trait and advance our understanding of the genetic mechanisms underlying osteoporotic fracture.
format Online
Article
Text
id pubmed-7388689
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-73886892020-08-07 Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density He, Pei Meng, Xiang-He Zhang, Xiao Lin, Xu Zhang, Qiang Jiang, Ri-Li Schiller, Martin R. Deng, Fei-Yan Deng, Hong-Wen Front Genet Genetics BACKGROUND: Genome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the SNPs or putative causal SNPs associated with eBMD were also associated with FNK-BMD. METHODS: Novel loci associated with eBMD and FNK-BMD were identified by the genetic pleiotropic conditional false discovery rate (cFDR) method. Shared putative causal variants between eBMD and FNK-BMD and putative causal SNPs for each trait were identified by the colocalization method. Mendelian randomization analysis addresses the causal relationship between eBMD/FNK-BMD and fracture. RESULTS: We identified 9,500 (cFDR < 9.8E-6), 137 (cFDR < 8.9E-4) and 124 SNPs associated with eBMD, FNK-BMD, and both eBMD and FNK-BMD, respectively, with 37 genomic regions where there was a SNP that influences both eBMD and FNK-BMD. Most genomic regions only contained putative causal SNPs associated with eBMD and 3 regions contained two distinct putative causal SNPs influenced both traits, respectively. We demonstrated a causal effect of FNK-BMD/eBMD on fracture. CONCLUSION: Most of SNPs or putative causal SNPs associated with FNK-BMD were also associated with eBMD. However, most of SNPs or putative causal SNPs associated with eBMD were not associated with FNK-BMD. The novel variants we identified may help to account for the additional proportion of variance of each trait and advance our understanding of the genetic mechanisms underlying osteoporotic fracture. Frontiers Media S.A. 2020-07-22 /pmc/articles/PMC7388689/ /pubmed/32774344 http://dx.doi.org/10.3389/fgene.2020.00772 Text en Copyright © 2020 He, Meng, Zhang, Lin, Zhang, Jiang, Schiller, Deng and Deng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
He, Pei
Meng, Xiang-He
Zhang, Xiao
Lin, Xu
Zhang, Qiang
Jiang, Ri-Li
Schiller, Martin R.
Deng, Fei-Yan
Deng, Hong-Wen
Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title_full Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title_fullStr Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title_full_unstemmed Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title_short Identifying Pleiotropic SNPs Associated With Femoral Neck and Heel Bone Mineral Density
title_sort identifying pleiotropic snps associated with femoral neck and heel bone mineral density
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388689/
https://www.ncbi.nlm.nih.gov/pubmed/32774344
http://dx.doi.org/10.3389/fgene.2020.00772
work_keys_str_mv AT hepei identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT mengxianghe identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT zhangxiao identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT linxu identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT zhangqiang identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT jiangrili identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT schillermartinr identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT dengfeiyan identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity
AT denghongwen identifyingpleiotropicsnpsassociatedwithfemoralneckandheelbonemineraldensity