The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis
Background Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished. Methods This study utilized Mendelian Randomization (MR) analysis to explore the causal re...
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| Veröffentlicht in: | Endocrine 2024-10, Vol.86 (1), p.380-390 |
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| creator | Mao, Rumeng Peng, Luyao Zhang, Youqian Li, Lin Ren, Yanrui |
| description | Background
Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished.
Methods
This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases.
Results
LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (r
g
range: −0.82 to 0.76, all
P
|
| doi_str_mv | 10.1007/s12020-024-03904-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3065981929</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3112100668</sourcerecordid><originalsourceid>FETCH-LOGICAL-c256t-e39a3ab4dde9e85fcb8f445450700404d5dea09f79099f2b945d841533d5c7aa3</originalsourceid><addsrcrecordid>eNp9kc1PFTEUxRsDEUT_ARekCRs3o7dfM1N2hPiVYNjguum0d56FmfbRzjN57vzPLTxQ4oJVb3N-57S5h5C3DN4zgO5DYRw4NMBlA0KDbPgLcsiU0g1Ufe_JfEBelXINwDlvu5fkQPS9Yq2Uh-T31Q-kYV5bt9A00iFFpHOImO1EPcYSli1NkS6VyqHc3DGjnaYQV6cUf4aKOKRjTjNdYcQlOOpSzjjZJVSbjZ5-w-hxCjbSXK9pDr8eNTttSyivyX5NLPjm4Twi3z99vDr_0lxcfv56fnbROK7apUGhrbCD9B419mp0Qz9KqaSCDkCC9MqjBT12GrQe-aCl8r1kSgivXGetOCLvdrnrnG43WBYzh-JwmmzEtClGQKt0zzTXFT35D71Om1z_WynGeF1o2_aV4jvK5VRKxtGsc5ht3hoG5q4gsyvI1ILMfUGGV9PxQ_RmmNH_tTw2UgGxA0qV4grzv7efif0DHrScTg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3112100668</pqid></control><display><type>article</type><title>The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis</title><source>MEDLINE</source><source>Springer LINK 全文期刊数据库</source><creator>Mao, Rumeng ; Peng, Luyao ; Zhang, Youqian ; Li, Lin ; Ren, Yanrui</creator><creatorcontrib>Mao, Rumeng ; Peng, Luyao ; Zhang, Youqian ; Li, Lin ; Ren, Yanrui</creatorcontrib><description>Background
Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished.
Methods
This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases.
Results
LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (r
g
range: −0.82 to 0.76, all
P
< 0.05). IVW analysis, with False Discovery Rate (FDR) correction, showed a protective causal effect of total body BMD (OR = 0.85, 95% CI 0.82–0.88,
P
= 7.63 × 10
−17
,
P
FDR
= 1.91 × 10
−16
), femoral neck BMD (OR = 0.81, 95% CI 0.75–0.88,
P
= 3.33 × 10
−7
,
P
FDR
= 5.55 × 10
−7
), lumbar spine BMD (OR = 0.85, 95% CI 0.79–0.91,
P
= 9.56 × 10
−7
,
P
FDR
= 1.20 × 10
−6
), and heel BMD (OR = 0.82, 95% CI 0.79–0.81,
P
= 1.69 × 10
−39
,
P
FDR
= 8.45 × 10
−39
) on falling risk. No causal relationship was found for forearm BMD (OR = 1.02, 95% CI 0.94–1.11,
P
= 0.64,
P
FDR
= 0.64). Replication datasets and CAUSE analysis provided causal evidence consistent with the main findings.
Conclusion
The study established a causal relationship between BMD at four different sites and the risk of falling, highlighting potential areas for targeted prevention strategies.</description><identifier>ISSN: 1559-0100</identifier><identifier>ISSN: 1355-008X</identifier><identifier>EISSN: 1559-0100</identifier><identifier>DOI: 10.1007/s12020-024-03904-2</identifier><identifier>PMID: 38851644</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Accidental Falls - statistics & numerical data ; Bone density ; Bone Density - genetics ; Bone mineral density ; Diabetes ; Endocrinology ; Female ; Femur Neck - diagnostic imaging ; Genetic analysis ; Humanities and Social Sciences ; Humans ; Internal Medicine ; Linkage analysis ; Linkage Disequilibrium ; Male ; Medicine ; Medicine & Public Health ; Mendelian Randomization Analysis ; multidisciplinary ; Original Article ; Osteoporosis - genetics ; Pleiotropy ; Polymorphism, Single Nucleotide ; Risk Factors ; Science ; Sensitivity analysis ; Spine (lumbar)</subject><ispartof>Endocrine, 2024-10, Vol.86 (1), p.380-390</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c256t-e39a3ab4dde9e85fcb8f445450700404d5dea09f79099f2b945d841533d5c7aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12020-024-03904-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12020-024-03904-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38851644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Rumeng</creatorcontrib><creatorcontrib>Peng, Luyao</creatorcontrib><creatorcontrib>Zhang, Youqian</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Ren, Yanrui</creatorcontrib><title>The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis</title><title>Endocrine</title><addtitle>Endocrine</addtitle><addtitle>Endocrine</addtitle><description>Background
Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished.
Methods
This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases.
Results
LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (r
g
range: −0.82 to 0.76, all
P
< 0.05). IVW analysis, with False Discovery Rate (FDR) correction, showed a protective causal effect of total body BMD (OR = 0.85, 95% CI 0.82–0.88,
P
= 7.63 × 10
−17
,
P
FDR
= 1.91 × 10
−16
), femoral neck BMD (OR = 0.81, 95% CI 0.75–0.88,
P
= 3.33 × 10
−7
,
P
FDR
= 5.55 × 10
−7
), lumbar spine BMD (OR = 0.85, 95% CI 0.79–0.91,
P
= 9.56 × 10
−7
,
P
FDR
= 1.20 × 10
−6
), and heel BMD (OR = 0.82, 95% CI 0.79–0.81,
P
= 1.69 × 10
−39
,
P
FDR
= 8.45 × 10
−39
) on falling risk. No causal relationship was found for forearm BMD (OR = 1.02, 95% CI 0.94–1.11,
P
= 0.64,
P
FDR
= 0.64). Replication datasets and CAUSE analysis provided causal evidence consistent with the main findings.
Conclusion
The study established a causal relationship between BMD at four different sites and the risk of falling, highlighting potential areas for targeted prevention strategies.</description><subject>Accidental Falls - statistics & numerical data</subject><subject>Bone density</subject><subject>Bone Density - genetics</subject><subject>Bone mineral density</subject><subject>Diabetes</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Femur Neck - diagnostic imaging</subject><subject>Genetic analysis</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Linkage analysis</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mendelian Randomization Analysis</subject><subject>multidisciplinary</subject><subject>Original Article</subject><subject>Osteoporosis - genetics</subject><subject>Pleiotropy</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><subject>Science</subject><subject>Sensitivity analysis</subject><subject>Spine (lumbar)</subject><issn>1559-0100</issn><issn>1355-008X</issn><issn>1559-0100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1PFTEUxRsDEUT_ARekCRs3o7dfM1N2hPiVYNjguum0d56FmfbRzjN57vzPLTxQ4oJVb3N-57S5h5C3DN4zgO5DYRw4NMBlA0KDbPgLcsiU0g1Ufe_JfEBelXINwDlvu5fkQPS9Yq2Uh-T31Q-kYV5bt9A00iFFpHOImO1EPcYSli1NkS6VyqHc3DGjnaYQV6cUf4aKOKRjTjNdYcQlOOpSzjjZJVSbjZ5-w-hxCjbSXK9pDr8eNTttSyivyX5NLPjm4Twi3z99vDr_0lxcfv56fnbROK7apUGhrbCD9B419mp0Qz9KqaSCDkCC9MqjBT12GrQe-aCl8r1kSgivXGetOCLvdrnrnG43WBYzh-JwmmzEtClGQKt0zzTXFT35D71Om1z_WynGeF1o2_aV4jvK5VRKxtGsc5ht3hoG5q4gsyvI1ILMfUGGV9PxQ_RmmNH_tTw2UgGxA0qV4grzv7efif0DHrScTg</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Mao, Rumeng</creator><creator>Peng, Luyao</creator><creator>Zhang, Youqian</creator><creator>Li, Lin</creator><creator>Ren, Yanrui</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20241001</creationdate><title>The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis</title><author>Mao, Rumeng ; Peng, Luyao ; Zhang, Youqian ; Li, Lin ; Ren, Yanrui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-e39a3ab4dde9e85fcb8f445450700404d5dea09f79099f2b945d841533d5c7aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Accidental Falls - statistics & numerical data</topic><topic>Bone density</topic><topic>Bone Density - genetics</topic><topic>Bone mineral density</topic><topic>Diabetes</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Femur Neck - diagnostic imaging</topic><topic>Genetic analysis</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Linkage analysis</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mendelian Randomization Analysis</topic><topic>multidisciplinary</topic><topic>Original Article</topic><topic>Osteoporosis - genetics</topic><topic>Pleiotropy</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><topic>Science</topic><topic>Sensitivity analysis</topic><topic>Spine (lumbar)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Rumeng</creatorcontrib><creatorcontrib>Peng, Luyao</creatorcontrib><creatorcontrib>Zhang, Youqian</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Ren, Yanrui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Rumeng</au><au>Peng, Luyao</au><au>Zhang, Youqian</au><au>Li, Lin</au><au>Ren, Yanrui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis</atitle><jtitle>Endocrine</jtitle><stitle>Endocrine</stitle><addtitle>Endocrine</addtitle><date>2024-10-01</date><risdate>2024</risdate><volume>86</volume><issue>1</issue><spage>380</spage><epage>390</epage><pages>380-390</pages><issn>1559-0100</issn><issn>1355-008X</issn><eissn>1559-0100</eissn><abstract>Background
Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished.
Methods
This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases.
Results
LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (r
g
range: −0.82 to 0.76, all
P
< 0.05). IVW analysis, with False Discovery Rate (FDR) correction, showed a protective causal effect of total body BMD (OR = 0.85, 95% CI 0.82–0.88,
P
= 7.63 × 10
−17
,
P
FDR
= 1.91 × 10
−16
), femoral neck BMD (OR = 0.81, 95% CI 0.75–0.88,
P
= 3.33 × 10
−7
,
P
FDR
= 5.55 × 10
−7
), lumbar spine BMD (OR = 0.85, 95% CI 0.79–0.91,
P
= 9.56 × 10
−7
,
P
FDR
= 1.20 × 10
−6
), and heel BMD (OR = 0.82, 95% CI 0.79–0.81,
P
= 1.69 × 10
−39
,
P
FDR
= 8.45 × 10
−39
) on falling risk. No causal relationship was found for forearm BMD (OR = 1.02, 95% CI 0.94–1.11,
P
= 0.64,
P
FDR
= 0.64). Replication datasets and CAUSE analysis provided causal evidence consistent with the main findings.
Conclusion
The study established a causal relationship between BMD at four different sites and the risk of falling, highlighting potential areas for targeted prevention strategies.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38851644</pmid><doi>10.1007/s12020-024-03904-2</doi><tpages>11</tpages></addata></record> |
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| subjects | Accidental Falls - statistics & numerical data Bone density Bone Density - genetics Bone mineral density Diabetes Endocrinology Female Femur Neck - diagnostic imaging Genetic analysis Humanities and Social Sciences Humans Internal Medicine Linkage analysis Linkage Disequilibrium Male Medicine Medicine & Public Health Mendelian Randomization Analysis multidisciplinary Original Article Osteoporosis - genetics Pleiotropy Polymorphism, Single Nucleotide Risk Factors Science Sensitivity analysis Spine (lumbar) |
| title | The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis |
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