Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight.
Birth weight
Bone mineral density
Conditional false discovery rate
Osteoporosis
Pleiotropy
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
17
06
2021
accepted:
04
11
2021
revised:
13
10
2021
pubmed:
23
3
2022
medline:
20
5
2022
entrez:
22
3
2022
Statut:
ppublish
Résumé
An increasing number of epidemiological studies have suggested that birth weight (BW) may be a determinant of bone health later in life, although the underlying genetic mechanism remains unclear. Here, we applied a pleiotropic conditional false discovery rate (cFDR) approach to the genome-wide association study (GWAS) summary statistics for lumbar spine bone mineral density (LS BMD) and BW, aiming to identify novel susceptibility variants shared between these two traits. We detected 5 novel potential pleiotropic loci which are located at or near 7 different genes (NTAN1, PDXDC1, CACNA1G, JAG1, FAT1P1, CCDC170, ESR1), among which PDXDC1 and FAT1P1 have not previously been linked to these phenotypes. To partially validate the findings, we demonstrated that the expression of PDXDC1 was dramatically reduced in ovariectomized (OVX) mice in comparison with sham-operated (SHAM) mice in both the growth plate and trabecula bone. Furthermore, immunohistochemistry assay with serial sections showed that both osteoclasts and osteoblasts express PDXDC1, supporting its potential role in bone metabolism. In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development. KEY MESSAGES : We investigated pleiotropy-informed enrichment between LS BMD and BW. We identified genetic variants related to both LS BMD and BW by utilizing a cFDR approach. PDXDC1 is a novel pleiotropic gene which may be related to both LS BMD and BW. Elevated expression of PDXDC1 is related to higher BMD and lower ratio n-6/n-3 PUFA indicating a bone protective effect of PDXDC1.
Identifiants
pubmed: 35314877
doi: 10.1007/s00109-021-02165-0
pii: 10.1007/s00109-021-02165-0
pmc: PMC9110509
doi:
Substances chimiques
Cacna1g protein, mouse
0
Calcium Channels, T-Type
0
Carboxy-Lyases
EC 4.1.1.-
Pdxdc1 protein, mouse
EC 4.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
723-734Subventions
Organisme : foundation for the national institutes of health
ID : R01AR057049
Organisme : foundation for the national institutes of health
ID : R01AR059781
Organisme : foundation for the national institutes of health
ID : R01MH107354
Organisme : foundation for the national institutes of health
ID : R01MH104680
Organisme : foundation for the national institutes of health
ID : R01GM109068
Organisme : foundation for the national institutes of health
ID : U19AG055373
Organisme : foundation for the national institutes of health
ID : R01AR069055
Informations de copyright
© 2022. The Author(s).
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