Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density

GEFOS-seq Consortium, Scott Wilson

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Abstract

Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p=1.20×10(-8), FHS p=0.05 for trochanter BMD; rs9287237, discovery p=3.55×10(-7), FHS p=9.20×10(-3) for trochanter BMD, GEFOS p=0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p=7.48×10(-7), FHS p=0.10 for inter-trochanter BMD, GEFOS p=0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p=3.09×10(-6), FHS p=8.50×10(-3), GEFOS p=1.23×10(-24) for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p=1.64×10(-6), GEFOS p=1.69×10(-3) for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p=8.79×10(-7), GEFOS p=2.61×10(-7) for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBone
Volume91
DOIs
Publication statusPublished - Oct 2016

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Genome-Wide Association Study
Bone Density
Meta-Analysis
Hip
Femur
Femur Neck
Genes
Spine
Bone Development
Forearm
Osteoporosis
Bone Fractures
Computer Simulation
Single Nucleotide Polymorphism

Cite this

@article{f2152a4283ff4f78b05806bb3a1216d0,
title = "Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density",
abstract = "Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p=1.20×10(-8), FHS p=0.05 for trochanter BMD; rs9287237, discovery p=3.55×10(-7), FHS p=9.20×10(-3) for trochanter BMD, GEFOS p=0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p=7.48×10(-7), FHS p=0.10 for inter-trochanter BMD, GEFOS p=0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p=3.09×10(-6), FHS p=8.50×10(-3), GEFOS p=1.23×10(-24) for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p=1.64×10(-6), GEFOS p=1.69×10(-3) for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p=8.79×10(-7), GEFOS p=2.61×10(-7) for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.",
keywords = "Adult, Bone Density/genetics, Chromosomes, Human, Pair 1/genetics, Chromosomes, Human, Pair 2/genetics, Female, Gene Regulatory Networks, Genetic Loci, Genome-Wide Association Study, Hip/pathology, Humans, Male, Middle Aged, Molecular Sequence Annotation, Polymorphism, Single Nucleotide/genetics, Reproducibility of Results",
author = "{GEFOS-seq Consortium} and Yu-Fang Pei and Wen-Zhu Hu and Rong Hai and Xiu-Yan Wang and Shu Ran and Yong Lin and Hui Shen and Qing Tian and Shu-Feng Lei and Yong-Hong Zhang and Papasian, {Christopher J} and Hong-Wen Deng and Lei Zhang and Scott Wilson",
year = "2016",
month = "10",
doi = "10.1016/j.bone.2016.07.004",
language = "English",
volume = "91",
pages = "1--10",
journal = "Bone",
issn = "8756-3282",
publisher = "Academic Press",

}

Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density. / GEFOS-seq Consortium ; Wilson, Scott.

In: Bone, Vol. 91, 10.2016, p. 1-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density

AU - GEFOS-seq Consortium

AU - Pei, Yu-Fang

AU - Hu, Wen-Zhu

AU - Hai, Rong

AU - Wang, Xiu-Yan

AU - Ran, Shu

AU - Lin, Yong

AU - Shen, Hui

AU - Tian, Qing

AU - Lei, Shu-Feng

AU - Zhang, Yong-Hong

AU - Papasian, Christopher J

AU - Deng, Hong-Wen

AU - Zhang, Lei

AU - Wilson, Scott

PY - 2016/10

Y1 - 2016/10

N2 - Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p=1.20×10(-8), FHS p=0.05 for trochanter BMD; rs9287237, discovery p=3.55×10(-7), FHS p=9.20×10(-3) for trochanter BMD, GEFOS p=0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p=7.48×10(-7), FHS p=0.10 for inter-trochanter BMD, GEFOS p=0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p=3.09×10(-6), FHS p=8.50×10(-3), GEFOS p=1.23×10(-24) for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p=1.64×10(-6), GEFOS p=1.69×10(-3) for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p=8.79×10(-7), GEFOS p=2.61×10(-7) for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.

AB - Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p=1.20×10(-8), FHS p=0.05 for trochanter BMD; rs9287237, discovery p=3.55×10(-7), FHS p=9.20×10(-3) for trochanter BMD, GEFOS p=0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p=7.48×10(-7), FHS p=0.10 for inter-trochanter BMD, GEFOS p=0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p=3.09×10(-6), FHS p=8.50×10(-3), GEFOS p=1.23×10(-24) for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p=1.64×10(-6), GEFOS p=1.69×10(-3) for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p=8.79×10(-7), GEFOS p=2.61×10(-7) for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.

KW - Adult

KW - Bone Density/genetics

KW - Chromosomes, Human, Pair 1/genetics

KW - Chromosomes, Human, Pair 2/genetics

KW - Female

KW - Gene Regulatory Networks

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Hip/pathology

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Sequence Annotation

KW - Polymorphism, Single Nucleotide/genetics

KW - Reproducibility of Results

U2 - 10.1016/j.bone.2016.07.004

DO - 10.1016/j.bone.2016.07.004

M3 - Article

VL - 91

SP - 1

EP - 10

JO - Bone

JF - Bone

SN - 8756-3282

ER -