Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study
Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship. Ut...
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| description | Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship.
Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA.
After conducting multiple tests (P |
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Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA.
After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction.
This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0307958</identifier><identifier>PMID: 39213290</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Age ; Arthritis ; Birth ; Births ; Body mass index ; Confidence intervals ; Contraceptives ; Demographic aspects ; Female ; Fertility ; Genome-wide association studies ; Genome-Wide Association Study ; Health aspects ; Heterogeneity ; Hormone replacement therapy ; Humans ; Menarche ; Menarche - genetics ; Mendelian Randomization Analysis ; Menopause ; Menstruation ; Middle Aged ; Observational studies ; Oral contraceptives ; Osteoarthritis ; Osteoarthritis - epidemiology ; Osteoarthritis - genetics ; Osteoarthritis, Knee - epidemiology ; Osteoarthritis, Knee - etiology ; Osteoarthritis, Knee - genetics ; Pleiotropy ; Polymorphism, Single Nucleotide ; Randomization ; Risk Factors ; Sensitivity analysis ; Sexual behavior ; Sexual intercourse ; Statistical analysis ; Statistical methods ; Variables</subject><ispartof>PloS one, 2024-08, Vol.19 (8), p.e0307958</ispartof><rights>Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c477t-8f3b56b02571f6c9ae9d003162f7d6ea626a6a4b889f65e171b4edadd6d9a8ef3</cites><orcidid>0009-0001-3738-6176</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0307958&type=printable$$EPDF$$P50$$Gplos$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307958$$EHTML$$P50$$Gplos$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,860,2096,2915,23845,27901,27902,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39213290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Xinzhe</creatorcontrib><creatorcontrib>Mei, Yifang</creatorcontrib><creatorcontrib>Zhou, Yihao</creatorcontrib><creatorcontrib>Liao, Zhichao</creatorcontrib><creatorcontrib>Zhang, Pengqi</creatorcontrib><creatorcontrib>Liu, Yichang</creatorcontrib><creatorcontrib>Han, Yixiao</creatorcontrib><creatorcontrib>Wang, Dongyan</creatorcontrib><title>Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship.
Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA.
After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction.
This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.</description><subject>Adult</subject><subject>Age</subject><subject>Arthritis</subject><subject>Birth</subject><subject>Births</subject><subject>Body mass index</subject><subject>Confidence intervals</subject><subject>Contraceptives</subject><subject>Demographic aspects</subject><subject>Female</subject><subject>Fertility</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Health aspects</subject><subject>Heterogeneity</subject><subject>Hormone replacement therapy</subject><subject>Humans</subject><subject>Menarche</subject><subject>Menarche - genetics</subject><subject>Mendelian Randomization Analysis</subject><subject>Menopause</subject><subject>Menstruation</subject><subject>Middle Aged</subject><subject>Observational studies</subject><subject>Oral contraceptives</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis - epidemiology</subject><subject>Osteoarthritis - genetics</subject><subject>Osteoarthritis, Knee - epidemiology</subject><subject>Osteoarthritis, Knee - etiology</subject><subject>Osteoarthritis, Knee - genetics</subject><subject>Pleiotropy</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Randomization</subject><subject>Risk Factors</subject><subject>Sensitivity analysis</subject><subject>Sexual behavior</subject><subject>Sexual intercourse</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Variables</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNktuO0zAQhiMEYpfCGyCIhITgosWJEx-4qyoOlRatxOnWmtjj1iWNi-2sWF6CVyal2WqLuODK1sw3_3h-T5Y9LsisoLx4tfF96KCd7XyHM0IJl7W4k50XkpZTVhJ699b9LHsQ44aQmgrG7mdnVJYFLSU5z34toI_Q5hCj1w6S813ubb7FLqbQD4mAu-BNr5O7wtyCTj7EfIDSGvPg4rc97WNCDyGtg0suvs7ned-5KwiDHubQmXzbt-kY-ICdwdZBl4ch57fu56FtTL25fpjds9BGfDSek-zL2zefF--nF5fvlov5xVRXnKepsLSpWUPKmheWaQkoDSG0YKXlhiGwkgGDqhFCWlZjwYumQgPGMCNBoKWT7OlBd9f6qEYvo6JESiJ5OTg3yZYHwnjYqF1wWwjXyoNTfwI-rNQwstMtqhobW5rGCtGIqtFMFrIyrKFaa26E4IPWi7Fb8N97jEltXdTYttCh7w9tBaE1rwf02V_ovx83UisY-rvO-hRA70XVXBDGWMVrMlAvTyjtu4Q_0mr48qiWnz7-P3v59ZR9fotdI7RpHX3b778xnoLVAdTBxxjQHn0siNpv8c1war_FatzioezJ6EHfbNEci27Wlv4GlezwRA</recordid><startdate>20240830</startdate><enddate>20240830</enddate><creator>Tan, Xinzhe</creator><creator>Mei, Yifang</creator><creator>Zhou, Yihao</creator><creator>Liao, Zhichao</creator><creator>Zhang, Pengqi</creator><creator>Liu, Yichang</creator><creator>Han, Yixiao</creator><creator>Wang, Dongyan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0009-0001-3738-6176</orcidid></search><sort><creationdate>20240830</creationdate><title>Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study</title><author>Tan, Xinzhe ; Mei, Yifang ; Zhou, Yihao ; Liao, Zhichao ; Zhang, Pengqi ; Liu, Yichang ; Han, Yixiao ; Wang, Dongyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-8f3b56b02571f6c9ae9d003162f7d6ea626a6a4b889f65e171b4edadd6d9a8ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Age</topic><topic>Arthritis</topic><topic>Birth</topic><topic>Births</topic><topic>Body mass index</topic><topic>Confidence intervals</topic><topic>Contraceptives</topic><topic>Demographic aspects</topic><topic>Female</topic><topic>Fertility</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Health aspects</topic><topic>Heterogeneity</topic><topic>Hormone replacement therapy</topic><topic>Humans</topic><topic>Menarche</topic><topic>Menarche - 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Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Xinzhe</au><au>Mei, Yifang</au><au>Zhou, Yihao</au><au>Liao, Zhichao</au><au>Zhang, Pengqi</au><au>Liu, Yichang</au><au>Han, Yixiao</au><au>Wang, Dongyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-08-30</date><risdate>2024</risdate><volume>19</volume><issue>8</issue><spage>e0307958</spage><pages>e0307958-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship.
Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA.
After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction.
This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39213290</pmid><doi>10.1371/journal.pone.0307958</doi><tpages>e0307958</tpages><orcidid>https://orcid.org/0009-0001-3738-6176</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-08, Vol.19 (8), p.e0307958 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3099097219 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Age Arthritis Birth Births Body mass index Confidence intervals Contraceptives Demographic aspects Female Fertility Genome-wide association studies Genome-Wide Association Study Health aspects Heterogeneity Hormone replacement therapy Humans Menarche Menarche - genetics Mendelian Randomization Analysis Menopause Menstruation Middle Aged Observational studies Oral contraceptives Osteoarthritis Osteoarthritis - epidemiology Osteoarthritis - genetics Osteoarthritis, Knee - epidemiology Osteoarthritis, Knee - etiology Osteoarthritis, Knee - genetics Pleiotropy Polymorphism, Single Nucleotide Randomization Risk Factors Sensitivity analysis Sexual behavior Sexual intercourse Statistical analysis Statistical methods Variables |
| title | Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study |
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