What you carry at this position in your DNA and what research says about it.
Osteoporosis Risk: 7/10 evidence, 20 publications.
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Sample genotype (not yours): G/G
Typical Osteoporosis and Fracture Risk
Presence of the common G allele on both chromosomes is associated with typical bone mineral density. This genotype does not carry the elevated risk of osteoporosis or bone fractures linked to the variant allele.
What this genotype means: Typical bone mineral density; Baseline risk of osteoporosis; Baseline risk of bone fractures.
Sample genotype (not yours): A/A
Increased Osteoporosis and Fracture Risk
Two copies of the A allele are associated with lower bone mineral density. This genotype is linked to an approximately 1.3-fold higher risk of osteoporosis and an increased risk of bone fractures.
What this genotype means: Lower bone mineral density; Increased risk of osteoporosis; Increased risk of bone fractures.
Sample genotype (not yours): G/A
Slightly Increased Osteoporosis and Fracture Risk
A single copy of the A allele is linked to a very slight reduction in bone mineral density. This can lead to a slightly higher risk of developing osteoporosis and experiencing bone fractures over time.
What this genotype means: Slightly lower bone mineral density; Slightly increased risk of osteoporosis; Slightly increased risk of bone fractures.
Gene function and biological role
Gene Function: LRP5 encodes the low-density lipoprotein receptor-related protein 5, which acts as a co-receptor in the canonical Wnt signaling pathway [1]. This pathway is a critical regulator of bone metabolism, guiding osteoblast development and bone formation [1]. Severe loss-of-function mutations in this gene cause osteoporosis-pseudoglioma syndrome, a rare condition characterized by extremely low bone mass and childhood fractures [2]. Conversely, other specific mutations in LRP5 can lead to high-bone-mass disorders [2]. In the general population, common variations in LRP5 help explain natural differences in peak bone mineral density and susceptibility to fractures [3].
Variant Impact: A missense change in exon 9 of the LRP5 gene defines the rs4988321 variant, substituting the amino acid valine with methionine at position 667 (p.Val667Met) [4]. This structural alteration in the LRP5 receptor is thought to reduce the efficiency of Wnt signaling, leading to decreased bone mineral density [4]. The G allele represents the typical valine residue, while the rarer A allele introduces methionine and acts as the risk factor [5]. Multiple large-scale genetic studies have linked the A allele to lower bone mineral density across various skeletal sites, including the spine and femoral neck [5]. Consequently, carriers of this minor variant face an elevated risk of developing osteoporosis and experiencing bone fractures [6].
Key Insight: The negative impact of the A allele on spine bone mineral density is most pronounced in individuals with low dietary calcium intake, while adequate calcium intake may help offset this genetic risk.
Location: LRP5. Chromosome 11 · 11q13.2 · 68.4 Mb
Estimated prevalence by population
Global 93.2%; European 89.9%; African 98.1%; East Asian 99.9%; South Asian 94.9%; Americas 91.7%; Ashkenazi 83.2%; Finnish 98.0%; Middle Eastern 78.1%; Amish 92.3%.
Estimated GG genotype frequency.
Global 6.6%; European 9.8%; African 1.9%; East Asian 0.1%; South Asian 5.0%; Americas 8.2%; Ashkenazi 16.0%; Finnish 2.0%; Middle Eastern 20.6%; Amish 7.6%.
Estimated GA genotype frequency.
Global 0.2%; European 0.3%; African < 0.1%; East Asian < 0.1%; South Asian 0.1%; Americas 0.2%; Ashkenazi 0.8%; Finnish < 0.1%; Middle Eastern 1.4%; Amish 0.2%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoporosis. Evidence: 7/10. Source: PMID 39024449. Typical Risk.
Bone Mineral Density. Evidence: 10/10. Source: PMID 41206123. Typical Density.
Bone Fracture Risk. Evidence: 8/10. Source: PMID 37919453. Typical Risk.
Respiratory Health
Lung Function. Evidence: 8/10. Source: PMID 36914875. Typical Function.
Cardiovascular & Metabolic
Obesity & Body Composition
Hip Circumference. Evidence: 7/10. Source: PMID 34021172. Typical.
Showing effects for A/A genotype
Osteoporosis. Evidence: 7/10. Source: PMID 39024449. ~1.3x Increased Risk.
Bone Mineral Density. Evidence: 10/10. Source: PMID 41206123. Lower Density.
Bone Fracture Risk. Evidence: 8/10. Source: PMID 37919453. ~1.12x Increased Risk.
Lung Function. Evidence: 8/10. Source: PMID 36914875. Lower Function.
Hip Circumference. Evidence: 7/10. Source: PMID 34021172. Larger.
Showing effects for G/A genotype
Osteoporosis. Evidence: 7/10. Source: PMID 39024449. Slightly Increased.
Bone Mineral Density. Evidence: 10/10. Source: PMID 41206123. Slightly Lower.
Bone Fracture Risk. Evidence: 8/10. Source: PMID 37919453. Slightly Increased.
Lung Function. Evidence: 8/10. Source: PMID 36914875. Slightly Lower.
Hip Circumference. Evidence: 7/10. Source: PMID 34021172. Slightly Larger.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Globally, this genotype is the most common configuration, representing the baseline for bone health studies [1]. Individuals with two copies of the G allele produce the standard LRP5 receptor, which supports normal Wnt signaling and bone remodeling [2]. Large-scale genome-wide association studies show that this genotype is linked to typical bone mineral density across multiple skeletal sites, including the spine, hip, and heel [3]. Because it lacks the risk-associated methionine variant, this genotype is associated with a lower likelihood of developing osteoporosis compared to carrier genotypes [4]. Furthermore, clinical data indicate a typical baseline risk for bone fractures [5]. Maintaining a balanced diet with adequate calcium and regular weight-bearing exercise remains important to support this natural baseline [2].
Typical bone mineral density; Baseline risk of osteoporosis; Baseline risk of bone fractures.
Sample genotype: AA (Homozygous)
Representing a relatively rare genetic profile, this configuration features two copies of the variant A allele, which encodes methionine at position 667 of the LRP5 protein. Having two copies of this variant is associated with a more pronounced reduction in Wnt signaling pathway activity, which is essential for bone formation [1]. Clinical studies have consistently linked this genotype to significantly lower bone mineral density in the lumbar spine, femoral neck, and heel [2]. As a result, individuals with this genotype have an estimated 1.3-fold increased risk of developing osteoporosis [3]. The risk of experiencing bone fractures, particularly vertebral and forearm fractures, is also elevated [4]. Research highlights that maintaining high dietary calcium intake is especially beneficial for individuals with this genetic profile, as it can help counteract the reduction in spine bone density [5]. Regular weight-bearing exercise and routine bone density monitoring are often discussed in clinical guidelines for managing bone health [1].
Lower bone mineral density; Increased risk of osteoporosis; Increased risk of bone fractures.
Sample genotype: GA (Heterozygous)
Carrying one copy of the standard G allele and one copy of the variant A allele defines this heterozygous state. The presence of the A allele introduces a methionine residue in the LRP5 protein, which slightly dampens Wnt signaling efficiency in bone-forming cells [1]. Consequently, individuals with this genotype tend to have slightly lower bone mineral density in key areas like the spine and heel [2]. This reduction in bone density translates to a very slightly increased risk of osteoporosis [3]. There is also a corresponding slight increase in susceptibility to bone fractures, particularly under stress [4]. Interestingly, research suggests that the negative impact of this variant on spine bone density is most pronounced when dietary calcium intake is low [5]. Ensuring adequate calcium intake and engaging in regular physical activity may help mitigate this genetic tendency [1].
Slightly lower bone mineral density; Slightly increased risk of osteoporosis; Slightly increased risk of bone fractures.
Variants with shared genetic architecture
rs3736228 · LRP5 Gene · Chr 11 · Bone Density and Fractures
rs7524102 · ZBTB40 Gene · Chr 1 · Bone Density and Tissue Health
rs3018362 · TNFRSF11A Gene · Chr 18 · Bone Health Risk
LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders.
LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women.
An atlas of genetic determinants of forearm fracture.
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Content updated August 2026.
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