Two studies found the genetic loci behind femoral neck bone density — the specific measurement site a clinical DXA scan uses to diagnose osteoporosis.
What this condition connects to
Prevalence
Not applicable in the usual sense — femoral neck BMD is a continuously measured trait, not a diagnosis on its own, though low bone density is a major risk factor for osteoporotic fracture. The studies behind this page examined tens of thousands of people (Zheng et al. 2015, PMID:26367794; Pei et al. 2018, PMID:29499414).
Inheritance
Polygenic overall, though the EN1 variant found by Zheng et al. 2015 is a rare exception — a low-frequency variant with an effect size four times larger than typical common BMD loci.
Femoral neck bone mineral density is bone density measured at the neck of the femur, the narrow section just below the hip joint. It is the specific site a clinical DXA (bone density) scan reports on to diagnose osteoporosis, distinct from this site's separate pages on heel, total-body, and paediatric bone density.
A rare large-effect variant, and a broader confirming study
Zheng et al. 2015 combined whole-genome sequencing, whole-exome sequencing, and deep imputation across up to 53,236 people for bone density and 508,253 for fracture risk. The standout finding was a low-frequency variant near EN1 with an effect size four times larger than typical common BMD variants — also linked to lower fracture risk — and confirmed with a mouse model showing that losing EN1 causes low bone mass through high bone turnover. The study also found a second large-effect variant near WNT16. This page's rs3779381, near WNT16, is that paper's own finding.
Pei et al. 2018 jointly analysed an in-house study of 7,484 people and the GEFOS-seq study of 32,965 people, finding 2 novel loci (near MACROD2 and OSBPL2) and replicating 7 loci already reported for heel and total-body BMD. This page's other 6 variants — near SOX6, RSPO3, C6ORF97, RPS6KA5, SMAD3, and AXIN1 — come from that replicated-loci set, not the paper's two novel findings.
Clinical detail
How osteoporosis is actually diagnosed
Osteoporosis is diagnosed with a DXA bone density scan, not with genotype. None of the variants here is used clinically to diagnose low bone density or guide treatment decisions.
Bone density screening and osteoporosis treatment decisions follow clinical guidelines based on measured bone density and fracture risk factors — not the variants listed here.
Related variants MyGeneLog™ checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Femoral Neck Bone Mineral Density comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 8 of 8 linked studies with a resolved discovery ancestry.
It is bone density measured at the neck of the femur, just below the hip joint — the specific site a clinical DXA scan reports on to diagnose osteoporosis.
What did these two studies find?
Zheng et al. 2015 found a rare, large-effect variant near EN1 linked to bone density and fracture risk, confirmed in a mouse model, plus a second large-effect variant near WNT16. Pei et al. 2018 found two more novel loci and replicated seven already known from heel and total-body BMD research.
Does this page diagnose osteoporosis?
No. Osteoporosis is diagnosed with a DXA bone density scan, not genotype. This page describes population-level genetic contributions to bone density at this specific measurement site.
Why is femoral neck BMD a separate page from this site's other bone density pages?
Because it is measured at a different skeletal site than heel, total-body, or paediatric bone density, and is specifically the site used in clinical osteoporosis diagnosis.
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