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Integrating GWAS and Co-expression Network Data Identifies Bone Mineral Density Genes SPTBN1 and MARK3 and an Osteoblast Functional Module.

Cell systems | Jan 25, 2017

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. Genome-wide association studies (GWAS) for BMD have identified dozens of associations; yet, the genes responsible for most associations remain elusive. Here, we used a bone co-expression network to predict causal genes at BMD GWAS loci based on the premise that genes underlying a disease are often functionally related and functionally related genes are often co-expressed. By mapping genes implicated by BMD GWAS onto a bone co-expression network, we predicted and inferred the function of causal genes for 30 of 64 GWAS loci. We experimentally confirmed that two of the genes predicted to be causal, SPTBN1 and MARK3, are potentially responsible for the effects of GWAS loci on chromosomes 2p16.2 and 14q32.32, respectively. This approach provides a roadmap for the dissection of additional BMD GWAS associations. Furthermore, it should be applicable to GWAS data for a wide range of diseases.

Pubmed ID: 27866947 RIS Download

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Associated grants

  • Agency: NCRR NIH HHS, Id: U42 RR024244
  • Agency: NIDA NIH HHS, Id: R01 DA006227
  • Agency: NIMH NIH HHS, Id: R01 MH101782
  • Agency: NCATS NIH HHS, Id: UL1 TR001863
  • Agency: NIMH NIH HHS, Id: R01 MH101810
  • Agency: NIMH NIH HHS, Id: R01 MH101819
  • Agency: NIDA NIH HHS, Id: R01 DA033684
  • Agency: NIMH NIH HHS, Id: R01 MH090936
  • Agency: NHGRI NIH HHS, Id: U01 HG004080
  • Agency: NIMH NIH HHS, Id: R01 MH090951
  • Agency: NIMH NIH HHS, Id: R01 MH101820
  • Agency: NIMH NIH HHS, Id: R01 MH101825
  • Agency: NIMH NIH HHS, Id: R01 MH090948
  • Agency: NIMH NIH HHS, Id: R01 MH090941
  • Agency: NIMH NIH HHS, Id: R01 MH101822
  • Agency: NIAMS NIH HHS, Id: R01 AR057759
  • Agency: CCR NIH HHS, Id: HHSN261200800001C
  • Agency: NIMH NIH HHS, Id: R01 MH090937
  • Agency: NHGRI NIH HHS, Id: U01 HG004085
  • Agency: NHLBI NIH HHS, Id: HHSN268201000029C
  • Agency: NCI NIH HHS, Id: HHSN261200800001E
  • Agency: NIMH NIH HHS, Id: R01 MH101814

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