Association of 3q13.32 variants with hip trochanter and intertrochanter bone mineral density identified by a genome-wide association study.
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.



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).



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.



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 × 10-4for INT-BMD; discovery p = 1.35 × 10-7, replication p = 4.16 × 10-4for 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 × 10-4for TRO-BMD, closest gene CTNNB1) and 8q24 (rs7839059, discovery p = 2.28 × 10-7, replication p = 1.55 × 10-3for 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.



Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.
Department of Epidemiology and Health Statistics, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.
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YF
Pei
The Second Affiliated Hospital of Soochow University, Jiangsu, People's Republic of China.
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Xie
Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, People's Republic of China.
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Wang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.|Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 199 Ren-ai Rd., Suzhou City, Jiangsu Province, 215123, People's Republic of China.
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Hu
The Second Affiliated Hospital of Soochow University, Jiangsu, People's Republic of China.
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Li
Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
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Ran
Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
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Lin
Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, People's Republic of China.
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Hai
Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
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Shen
Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
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Tian
Department of Epidemiology and Health Statistics, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.
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Zhang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China.|Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 199 Ren-ai Rd., Suzhou City, Jiangsu Province, 215123, People's Republic of China.
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Lei
Department of Basic Medical Science, University of Missouri-Kansas City, Kansas City, MO, USA.
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Papasian
Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. hdeng2@tulane.edu.|Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St., Suite 2001, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.
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Deng
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Jiangsu, People's Republic of China. lzhang6@suda.edu.cn.|Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 199 Ren-ai Rd., Suzhou City, Jiangsu Province, 215123, People's Republic of China. lzhang6@suda.edu.cn.
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Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D005269:Femur / Q000473:pathology*; D005272:Femur Neck; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis; D010641:Phenotype
3q13.32; Genome-wide association study; Intertrochanter; Osteoporosis; Trochanter