What you carry at this position in your DNA and what research says about it.
Bone Density and Fractures: 8/10 evidence, 32 publications.
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Sample genotype (not yours): C/C
Typical Bone Density and Lower Fracture Risk
Optimal LRP5 receptor function is associated with the common C allele. This supports healthy bone mineral density and a lower risk of developing osteoporosis or experiencing bone fractures.
What this genotype means: Typical bone mineral density; Lower risk of osteoporosis; Lower risk of bone fractures.
Sample genotype (not yours): C/T
Moderately Increased Risk of Osteoporosis and Fractures
Slightly reduced LRP5 receptor activity is linked to the T allele. This can lead to lower bone mineral density and a moderately higher susceptibility to bone fractures over time.
What this genotype means: Slightly lower bone mineral density; Moderately increased risk of osteoporosis; Increased risk of bone fractures.
Sample genotype (not yours): T/T
Higher Risk of Osteoporosis and Bone Fractures
Significantly reduced LRP5 receptor function is associated with the TT genotype. This genetic profile is linked to lower bone mineral density and a higher risk of osteoporosis and skeletal fractures.
What this genotype means: Lower bone mineral density; Increased risk of osteoporosis; Higher risk of bone fractures.
Gene function and biological role
Gene Function: The LRP5 gene encodes a transmembrane low-density lipoprotein receptor-related protein that is crucial for bone biology. It acts as a co-receptor in the canonical Wnt signaling pathway, which regulates osteoblast differentiation and bone formation [1]. Mutations in this gene can lead to severe skeletal disorders, highlighting its essential role in maintaining bone mass [2]. Beyond bone development, LRP5 is also involved in lipid metabolism and glucose homeostasis [3]. This multi-functional receptor is expressed in various tissues, including bone, liver, and vascular endothelial cells [1].
Variant Impact: The rs3736228 variant, also known as Ala1330Val or A1330V, is a missense mutation in exon 18 of the LRP5 gene. This genetic change replaces the amino acid alanine with valine at position 1330 of the protein, which downregulates the cell surface receptor function of LRP5 [4]. This reduction in receptor activity impairs Wnt signaling, leading to decreased bone mineral density and weaker bone structure [5]. Multiple large-scale studies and meta-analyses have confirmed its significant impact on skeletal strength and fracture susceptibility [6]. The variant is relatively common, with the risk-associated T allele found in about 11% of the global population [5].
Key Insight: The LRP5 gene regulates bone density through the Wnt signaling pathway, and this specific variant can reduce receptor function, leading to a 30% increase in osteoporosis risk.
Location: LRP5. Chromosome 11 · 11q13.2 · 68.4 Mb
Estimated prevalence by population
Global 79.4%; European 73.7%; African 91.6%; East Asian 63.2%; South Asian 75.6%; Americas 71.3%; Ashkenazi 79.7%; Finnish 92.4%; Middle Eastern 67.7%; Amish 49.9%.
Estimated CC genotype frequency.
Global 19.1%; European 24.3%; African 8.2%; East Asian 32.6%; South Asian 22.7%; Americas 26.3%; Ashkenazi 19.1%; Finnish 7.5%; Middle Eastern 29.1%; Amish 41.5%.
Estimated CT genotype frequency.
Global 1.5%; European 2.0%; African 0.2%; East Asian 4.2%; South Asian 1.7%; Americas 2.4%; Ashkenazi 1.1%; Finnish 0.2%; Middle Eastern 3.1%; Amish 8.6%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoporosis. Evidence: 5/10. Source: PMID 18455228. Typical Risk.
Bone Fracture Risk. Evidence: 8/10. Source: PMID 30158200. Typical Risk.
Spine Bone Density. Evidence: 8/10. Source: PMID 34673960. Higher Density.
Lifestyle, Fitness & Aging
Muscle Strength & Power
Appendicular Lean Mass. Evidence: 6/10. Source: PMID 31761296. Higher Lean Mass.
Showing effects for C/T genotype
Osteoporosis. Evidence: 5/10. Source: PMID 18455228. ~1.3x Increased Risk.
Bone Fracture Risk. Evidence: 8/10. Source: PMID 30158200. ~1.06x Increased Risk.
Spine Bone Density. Evidence: 8/10. Source: PMID 34673960. Lower Density.
Appendicular Lean Mass. Evidence: 6/10. Source: PMID 31761296. Lower Lean Mass.
Showing effects for T/T genotype
Bone Fracture Risk. Evidence: 8/10. Source: PMID 30158200. ~1.12x Increased Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the alanine-encoding C allele represents the typical genetic baseline for bone health [1]. This genotype is associated with higher bone mineral density in both the lumbar spine and the femoral neck compared to carriers of the T allele [2]. Consequently, a lower risk of developing osteoporosis and suffering from osteoporotic fractures is observed [3]. Research indicates that the normal functioning of the LRP5 protein maintains robust Wnt signaling, which is essential for bone remodeling and strength [4]. Additionally, some studies suggest a positive association with appendicular lean mass, indicating a supportive role in overall body composition [5]. This means the body is better equipped to maintain skeletal integrity during aging. Regular physical activity further enhances this natural genetic advantage. Maintaining a balanced diet rich in calcium and vitamin D helps sustain these optimal bone density levels throughout life.
Typical bone mineral density; Lower risk of osteoporosis; Lower risk of bone fractures.
Sample genotype: CT (Heterozygous)
Carrying one copy of the T allele (valine variant) is associated with a moderate reduction in LRP5 receptor function, which can affect bone density [1]. Meta-analyses show that the CT genotype tends to correlate with lower bone mineral density in key areas like the lumbar spine and hip [2]. This reduction in bone density translates to a roughly 30% increase in the risk of developing osteoporosis [2]. Furthermore, the risk of experiencing osteoporotic fractures is elevated, with studies reporting an odds ratio of approximately 1.06 to 1.3 per risk allele [3]. Maintaining adequate calcium and vitamin D intake, along with regular weight-bearing exercise, is often recommended to help mitigate this genetic predisposition [4]. These lifestyle interventions are particularly important as bone density naturally declines with age. Monitoring bone health through periodic density scans can provide valuable insights for early prevention. Understanding this genetic risk allows for proactive steps to support skeletal strength.
Slightly lower bone mineral density; Moderately increased risk of osteoporosis; Increased risk of bone fractures.
Sample genotype: TT (Homozygous)
Carrying two copies of the valine-encoding T allele significantly downregulates LRP5 receptor activity [1]. This reduction in receptor function impairs the canonical Wnt pathway, leading to lower peak bone mass and accelerated bone loss [2]. Multiple studies have demonstrated that the TT genotype correlates with significantly lower bone mineral density in the lumbar spine and femoral neck [3]. This genetic profile is associated with a 30% or higher increase in the risk of osteoporosis and a corresponding rise in fracture risk [4]. Interestingly, some research suggests that men with this genotype might show different bone density responses to specific osteoporosis treatments, highlighting the role of personalized medicine [5]. Proactive bone-strengthening strategies, such as resistance training and avoiding smoking, are highly beneficial for individuals with this profile. Consulting with a healthcare provider about bone density monitoring can help guide personalized prevention plans. Early lifestyle adjustments can significantly offset the genetic tendency toward weaker bones.
Lower bone mineral density; Increased risk of osteoporosis; Higher risk of bone fractures.
Variants with shared genetic architecture
rs4988321 · LRP5 Gene · Chr 11 · Osteoporosis Risk
rs11898505 · SPTBN1 Gene · Chr 2 · Bone Density
rs6426749 · ZBTB40 Gene · Chr 1 · Bone Mineral Density
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.
LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men.
Content updated August 2026.
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