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The analysis of causal relationships between blood lipid levels and BMD
Bone mineral density (BMD) and lipid levels are two of the most extensively studied risk factors for common diseases of aging, such as cardiovascular disease (CVD) and osteoporosis (OP). These two risk factors are also correlated with each other, but little is known about the molecular mechanisms be...
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| Published in: | PloS one 2019-02, Vol.14 (2), p.e0212464-e0212464 |
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| creator | Cherny, Stacey S Freidin, Maxim B Williams, Frances M K Livshits, Gregory |
| description | Bone mineral density (BMD) and lipid levels are two of the most extensively studied risk factors for common diseases of aging, such as cardiovascular disease (CVD) and osteoporosis (OP). These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. While results involving the twin modelling and MR analyses with metabolites were unable to establish a causal link between metabolite levels and either lipids or BMD, MR analyses of BMD and lipids suggest that lipid levels have a causal impact on BMD, which is consistent with findings from clinical trials of lipid-lowering drugs, which have also increased BMD. |
| doi_str_mv | 10.1371/journal.pone.0212464 |
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These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. While results involving the twin modelling and MR analyses with metabolites were unable to establish a causal link between metabolite levels and either lipids or BMD, MR analyses of BMD and lipids suggest that lipid levels have a causal impact on BMD, which is consistent with findings from clinical trials of lipid-lowering drugs, which have also increased BMD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0212464</identifier><identifier>PMID: 30794634</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aging ; Analysis ; Androsterone - metabolism ; Anticholesteremic agents ; Biocompatibility ; Biology and Life Sciences ; Biomedical materials ; Biosynthesis ; Bone density ; Bone Density - genetics ; Bone Density - physiology ; Bone mineral density ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - metabolism ; Causality ; Causation ; Cholesterol ; Chromosomes ; Clinical trials ; Correlation analysis ; Epidemiology ; Genetics ; Genome-Wide Association Study ; Health aspects ; Health risks ; Humans ; Lipid metabolism ; Lipids ; Lipids - blood ; Lipids - genetics ; Medical research ; Medicine ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Modelling ; Molecular modelling ; Osteoporosis ; Osteoporosis - etiology ; Osteoporosis - genetics ; Osteoporosis - metabolism ; Phenotype ; Physical Sciences ; Physiological aspects ; Risk analysis ; Risk Factors ; Studies ; Systematic review ; Twins ; Twins, Dizygotic ; Twins, Monozygotic ; United Kingdom</subject><ispartof>PloS one, 2019-02, Vol.14 (2), p.e0212464-e0212464</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Cherny et al. 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These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. 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Academic</collection><collection>PubMed Central (Full Participant titles)</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>Cherny, Stacey S</au><au>Freidin, Maxim B</au><au>Williams, Frances M K</au><au>Livshits, Gregory</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The analysis of causal relationships between blood lipid levels and BMD</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-02-22</date><risdate>2019</risdate><volume>14</volume><issue>2</issue><spage>e0212464</spage><epage>e0212464</epage><pages>e0212464-e0212464</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Competing Interests: The authors have declared that no competing interests exist.</notes><abstract>Bone mineral density (BMD) and lipid levels are two of the most extensively studied risk factors for common diseases of aging, such as cardiovascular disease (CVD) and osteoporosis (OP). These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. While results involving the twin modelling and MR analyses with metabolites were unable to establish a causal link between metabolite levels and either lipids or BMD, MR analyses of BMD and lipids suggest that lipid levels have a causal impact on BMD, which is consistent with findings from clinical trials of lipid-lowering drugs, which have also increased BMD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30794634</pmid><doi>10.1371/journal.pone.0212464</doi><tpages>e0212464</tpages><orcidid>https://orcid.org/0000-0002-0269-3352</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aging Analysis Androsterone - metabolism Anticholesteremic agents Biocompatibility Biology and Life Sciences Biomedical materials Biosynthesis Bone density Bone Density - genetics Bone Density - physiology Bone mineral density Cardiovascular diseases Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Cardiovascular Diseases - metabolism Causality Causation Cholesterol Chromosomes Clinical trials Correlation analysis Epidemiology Genetics Genome-Wide Association Study Health aspects Health risks Humans Lipid metabolism Lipids Lipids - blood Lipids - genetics Medical research Medicine Medicine and Health Sciences Metabolism Metabolites Modelling Molecular modelling Osteoporosis Osteoporosis - etiology Osteoporosis - genetics Osteoporosis - metabolism Phenotype Physical Sciences Physiological aspects Risk analysis Risk Factors Studies Systematic review Twins Twins, Dizygotic Twins, Monozygotic United Kingdom |
| title | The analysis of causal relationships between blood lipid levels and BMD |
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