Bmd46^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Bmd46^C3H/HeJ
• Name: bone mineral density 46, males; C3H/HeJ
• MGI ID: MGI:6382966
• QTL: Bmd46 Location: Chr3:52407421-52407421 bp Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:275448

Bone mineral density (BMD) is a strong predictor of osteoporotic fracture. It is also one of the most heritable disease-associated quantitative traits. The authors performed a genome-wide association study (GWAS) in a panel of inbred strains to identify associations influencing BMD.

GWAS was performed for total body BMD in 26 classical (non wild-derived) inbred strains at 12 months of age. Genome scans were performed separately for each sex using the Efficient Mixed Model Algorithm (EMMA) to account for population stratification. For the analysis BMD was rankZ transformed. SNPs were obtained from strains genotyped on the Mouse Diversity Array (http://churchill-lab.jax.org/website/MDA). SNPs with a minor allele frequency ^{0.05 were removed, leaving 228,085 SNPs. These SNPs were used to generate a kinship using the emma.kinship R script available in the EMMA R package (available at http://mouse.cs.ucla.edu/emma/). The emma.REML.t function of EMMA was used to perform all mapping analyses. All genome coordinates are relative to GRCm38/mm10.}

In female mice, a significant (permutation determined threshold of -log10 (P)6) association was identified on Chromosome 3. In males, significant (permutation determined threshold of -log10(P)>5.9) loci were identified on Chromosomes 2 and 3. The authors selected the Chromosome 3 locus for further investigation because it was the most significant and the only one identified in both sexes.

Chromosome 3 harbored two significant associations:

Bmd46 (bone mineral density 46, males) maps to Chr 3 with a peak -log10(P) of 11.5 at 52.5 Mbp. There were 17 lead SNPs (the C57BL/6J reference allele was the minor allele at all SNPs with a frequency of 0.42), with the exact same strain distribution pattern at Bmd46. All 16 were polymorphic between C57BL/6J and C3H/HeJ.

Bmd47 (bone mineral density 47, females) maps to Chr 3 with a peak -log10(P) of 5.9 at 63.3 Mbp.

Candidate gene Lhfp was identified as a regulator of osteoblast activity and bone mass.

References

• Original: J:275448 Mesner LD, et al., Mouse genome-wide association and systems genetics identifies Lhfp as a regulator of bone mass. PLoS Genet. 2019 May;15(5):e1008123
• All: 1 reference(s)