What were the strongest cis-variants in the BMD loci?

Fourteen of the BMD-associated SNPs correlated with the expression of one or more of the nearby genes with P < 5×10−5 and were either the strongest cis-variants, or good surrogates thereof, for those genes (Supplementary Tables 14 and 15).

How many SNPs were found in the discovery and replication studies?

The meta-analysis of the 96 SNPs in the discovery and replication studies (n=83,894) yielded 64 replicating SNPs from 56 associated loci.

What were the significant SNPs of the X-chromosome?

The 96 variants included the 82 index SNPs representing each of the 82 loci reaching P<5×10−6 in Stage 1, 9 SNPs that lie within the same 2Mb windows as the 82 but which were independent from the main signal (secondary signals), and the top-five most associated SNPs of the X-chromosome (with P <5×10−5).

How many additional participants were tested for association with BMD?

The authors de-novo genotyped these 96 SNPs and tested them for association with BMD in up to 50,933 additional participants from 34 studies (see Online Methods).

What was the proportion of the fracture risk explained by FN-BMD?

The proportion of the fracture risk explained by FN-BMD was calculated from the regression coefficients as (βunadjusted - βBMDadjusted)/βunadjusted in a subset of replication samples for which both FNBMD and complete fracture information was available.

How do the gradients of risk for osteoporosis and fractures compare?

These gradients reach ORs of 1.56 for osteoporosis and 1.60 for fractures when comparing participants with the highest risk scores with those reflecting the mean score.

(PDF) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture (2012) | Karol Estrada

Q: What have the authors contributed in "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

The authors performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry. The authors report here the results of the largest effort to date searching for BMD loci in > 80,000 subjects and testing them for association with fracture in > 130,000 cases and controls. The authors identified 56 loci ( 32 novel ) associated with BMD atgenome-wide significant level ( P < 5×10−8 ).

Q: What future works have the authors mentioned in the paper "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

Further exploration of these loci with more detailed sequencing, gene expression, and translational studies will be required. In conclusion, these findings highlight the highly polygenic and complex nature underlying BMD variation, shedding light on the pathophysiological mechanisms underlying fracture susceptibility and harbouring potential for the future identification of drug targets for the treatment of osteoporosis.

Q: How many SNPs were removed from the meta-analysis?

45,46 SNPs present in less than three studies were removed from the meta-analysis yielding ~ 2.2 million SNPs in the final results.

Q: How many loci were found to be associated with a fracture?

In this fracture meta-analysis fourteen loci were significantly associated with any type of fracture at a Bonferroni level (P=5×10−4), of which five included novel BMD loci.

Q: How many SNPs were found in the discovery and replication studies?

The meta-analysis of the 96 SNPs in the discovery and replication studies (n=83,894) yielded 64 replicating SNPs from 56 associated loci.

Q: What were the significant SNPs of the X-chromosome?

The 96 variants included the 82 index SNPs representing each of the 82 loci reaching P<5×10−6 in Stage 1, 9 SNPs that lie within the same 2Mb windows as the 82 but which were independent from the main signal (secondary signals), and the top-five most associated SNPs of the X-chromosome (with P <5×10−5).

Q: How many additional participants were tested for association with BMD?

The authors de-novo genotyped these 96 SNPs and tested them for association with BMD in up to 50,933 additional participants from 34 studies (see Online Methods).

Q: How many individuals of European and East Asian ancestry were included in the meta-analysis?

The authors performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry.

Q: What was the proportion of the fracture risk explained by FN-BMD?

The proportion of the fracture risk explained by FN-BMD was calculated from the regression coefficients as (βunadjusted - βBMDadjusted)/βunadjusted in a subset of replication samples for which both FNBMD and complete fracture information was available.

Most frequently asked questions

1. What have the authors contributed in "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

The authors performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry.. The authors report here the results of the largest effort to date searching for BMD loci in > 80,000 subjects and testing them for association with fracture in > 130,000 cases and controls.. The authors identified 56 loci ( 32 novel ) associated with BMD atgenome-wide significant level ( P < 5×10−8 ).

2. What future works have the authors mentioned in the paper "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

Further exploration of these loci with more detailed sequencing, gene expression, and translational studies will be required.. In conclusion, these findings highlight the highly polygenic and complex nature underlying BMD variation, shedding light on the pathophysiological mechanisms underlying fracture susceptibility and harbouring potential for the future identification of drug targets for the treatment of osteoporosis.

3. How many SNPs were removed from the meta-analysis?

45,46 SNPs present in less than three studies were removed from the meta-analysis yielding ~ 2.2 million SNPs in the final results.

4. How many loci were found to be associated with a fracture?

In this fracture meta-analysis fourteen loci were significantly associated with any type of fracture at a Bonferroni level (P=5×10−4), of which five included novel BMD loci.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

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Most frequently asked questions

1. What have the authors contributed in "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

2. What future works have the authors mentioned in the paper "Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture" ?

3. How many SNPs were removed from the meta-analysis?

4. How many loci were found to be associated with a fracture?

5. What were the strongest cis-variants in the BMD loci?

6. How many SNPs were found in the discovery and replication studies?

7. What were the significant SNPs of the X-chromosome?

8. How many additional participants were tested for association with BMD?

9. How many individuals of European and East Asian ancestry were included in the meta-analysis?

10. What was the proportion of the fracture risk explained by FN-BMD?

11. How do the gradients of risk for osteoporosis and fractures compare?

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References

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