Association of 3q13.32 variants with hip trochanter and intertrochanter bone mineral density identified by a genome-wide association study.
Osteoporos Int
; 27(11): 3343-3354, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27311723
ABSTRACT
We performed a GWAS of trochanter and intertrochanter bone mineral density (BMD) in the Framingham Heart Study and replicated in three independent studies. Our results identified one novel locus around the associated variations at chromosomal region 3q13.32 and replicated two loci at chromosomal regions 3p21 and 8q24. Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis. INTRODUCTION:
Hip trochanter (TRO) and intertrochanter (INT) subregions have important clinical relevance to subtrochanteric and intertrochanteric fractures but have rarely been studied by genome-wide association studies (GWASs).METHODS:
Aiming to identify genomic loci associated with BMD variation at TRO and INT regions, we performed a GWAS utilizing the Framingham Heart Study (FHS, N = 6,912) as discovery sample and utilized the Women's Health Initiative (WHI) African-American subsample (N = 845), WHI Hispanic subsample (N = 446), and Omaha osteoporosis study (N = 971), for replication.RESULTS:
Combining the evidence from both the discovery and the replication samples, we identified one novel locus around the associated variations at chromosomal region 3q13.32 (rs1949542, discovery p = 6.16 × 10-8, replication p = 2.86 × 10-4 for INT-BMD; discovery p = 1.35 × 10-7, replication p = 4.16 × 10-4 for TRO-BMD, closest gene RP11-384F7.1). We also replicated two loci at chromosomal regions 3p21 (rs148725943, discovery p = 6.61 × 10-7, replication p = 5.22 × 10-4 for TRO-BMD, closest gene CTNNB1) and 8q24 (rs7839059, discovery p = 2.28 × 10-7, replication p = 1.55 × 10-3 for TRO-BMD, closest gene TNFRSF11B) that were reported previously. We demonstrated that the effects at both 3q13.32 and 3p21 were specific to the TRO, but not to the femoral neck and spine. In contrast, the effect at 8q24 was common to all the sites.CONCLUSION:
Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.Palabras clave
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1
Bases de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 3
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Densidad Ósea
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Fémur
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Sitios Genéticos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Osteoporos Int
Asunto de la revista:
METABOLISMO
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ORTOPEDIA
Año:
2016
Tipo del documento:
Article