Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization
Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction a...
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| creator | Dam, Veerle Onland-Moret, N. Charlotte Burgess, Stephen Chirlaque, Maria Dolores Peters, Sanne A.E Schuit, Ewoud Tikk, Kaja Weiderpass, Elisabete Oliver-Williams, Clare Wood, Angela M Tjønneland, Anne Dahm, Christina C Overvad, Kim Boutron-Rualt, Marie-Christine Schulze, Matthias B Trichopoulou, Antonia Ferrari, Pietro Masala, Giovanna Krogh, Vittorio Tumino, Rosario Matullo, Giuseppe Panico, Salvatore Boer, Jolanda M. A Verschuren, W.M. Monique Waaseth, Marit Pérez, María José Sánchez Amiano, Pilar Imaz, Liher Moreno-Iribas, Conchi Melander, Olle Harlid, Sophia Nordendahl, Maria Wennberg, Patrik Key, Timothy J Riboli, Elio Santiuste, Carmen Kaaks, Rudolf Katzke, Verena Langenberg, Claudia Wareham, Nicholas J Schunkert, Heribert Erdmann, Jeanette Willenborg, Christina Hengstenberg, Christian Kleber, Marcus E Delgado, Graciela März, Winfried Kanoni, Stavroula Dedoussis, George Deloukas, Panos Nikpay, Majid McPherson, Ruth Scholz, Markus Teren, Andrej Butterworth, Adam S van der Schouw, Yvonne T |
| description | Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart
disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.
Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk
factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men.
Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard
inverse-variance weighted (IVW) regression, and MR-Egger regression.
Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were
pooled for the different analyses.
Main Outcome Measures: CHD, CHD risk factors, and ANM.
Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in
women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were
found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging.
Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men. |
| doi_str_mv | 10.1210/clinem/dgac171 |
| format | Article |
| fullrecord | <record><control><sourceid>cristin</sourceid><recordid>TN_cdi_cristin_nora_10037_26342</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>10037_26342</sourcerecordid><originalsourceid>FETCH-cristin_nora_10037_263423</originalsourceid><addsrcrecordid>eNqFzLtOxDAQhWELgUS4tLTMC4T1OFms0CIuzTaIgi4a7CEMcuyVbS7L0xMkeqpTnE-_UmeoL9CgXrkgkeeVn8ihxT3V4NCvW4uD3VeN1gbbwZqnQ3VUypvW2PfrrlFfdxy5iqMQduC5cp6XiofM25z8u6vywUCTxAkoenApp0h5B69MuYKXwlT4CgiexUvmxS9_gPqZ2kLzNjBsOHoOQhEelkKa5Zt-0Yk6eKFQ-PRvj9X57c3j9X3rspQqcYwp04had3Y0l11vuv_FDzpjUuA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization</title><source>NORA - Norwegian Open Research Archives</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Dam, Veerle ; Onland-Moret, N. Charlotte ; Burgess, Stephen ; Chirlaque, Maria Dolores ; Peters, Sanne A.E ; Schuit, Ewoud ; Tikk, Kaja ; Weiderpass, Elisabete ; Oliver-Williams, Clare ; Wood, Angela M ; Tjønneland, Anne ; Dahm, Christina C ; Overvad, Kim ; Boutron-Rualt, Marie-Christine ; Schulze, Matthias B ; Trichopoulou, Antonia ; Ferrari, Pietro ; Masala, Giovanna ; Krogh, Vittorio ; Tumino, Rosario ; Matullo, Giuseppe ; Panico, Salvatore ; Boer, Jolanda M. A ; Verschuren, W.M. Monique ; Waaseth, Marit ; Pérez, María José Sánchez ; Amiano, Pilar ; Imaz, Liher ; Moreno-Iribas, Conchi ; Melander, Olle ; Harlid, Sophia ; Nordendahl, Maria ; Wennberg, Patrik ; Key, Timothy J ; Riboli, Elio ; Santiuste, Carmen ; Kaaks, Rudolf ; Katzke, Verena ; Langenberg, Claudia ; Wareham, Nicholas J ; Schunkert, Heribert ; Erdmann, Jeanette ; Willenborg, Christina ; Hengstenberg, Christian ; Kleber, Marcus E ; Delgado, Graciela ; März, Winfried ; Kanoni, Stavroula ; Dedoussis, George ; Deloukas, Panos ; Nikpay, Majid ; McPherson, Ruth ; Scholz, Markus ; Teren, Andrej ; Butterworth, Adam S ; van der Schouw, Yvonne T</creator><creatorcontrib>Dam, Veerle ; Onland-Moret, N. Charlotte ; Burgess, Stephen ; Chirlaque, Maria Dolores ; Peters, Sanne A.E ; Schuit, Ewoud ; Tikk, Kaja ; Weiderpass, Elisabete ; Oliver-Williams, Clare ; Wood, Angela M ; Tjønneland, Anne ; Dahm, Christina C ; Overvad, Kim ; Boutron-Rualt, Marie-Christine ; Schulze, Matthias B ; Trichopoulou, Antonia ; Ferrari, Pietro ; Masala, Giovanna ; Krogh, Vittorio ; Tumino, Rosario ; Matullo, Giuseppe ; Panico, Salvatore ; Boer, Jolanda M. A ; Verschuren, W.M. Monique ; Waaseth, Marit ; Pérez, María José Sánchez ; Amiano, Pilar ; Imaz, Liher ; Moreno-Iribas, Conchi ; Melander, Olle ; Harlid, Sophia ; Nordendahl, Maria ; Wennberg, Patrik ; Key, Timothy J ; Riboli, Elio ; Santiuste, Carmen ; Kaaks, Rudolf ; Katzke, Verena ; Langenberg, Claudia ; Wareham, Nicholas J ; Schunkert, Heribert ; Erdmann, Jeanette ; Willenborg, Christina ; Hengstenberg, Christian ; Kleber, Marcus E ; Delgado, Graciela ; März, Winfried ; Kanoni, Stavroula ; Dedoussis, George ; Deloukas, Panos ; Nikpay, Majid ; McPherson, Ruth ; Scholz, Markus ; Teren, Andrej ; Butterworth, Adam S ; van der Schouw, Yvonne T</creatorcontrib><description>Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart
disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.
Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk
factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men.
Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard
inverse-variance weighted (IVW) regression, and MR-Egger regression.
Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were
pooled for the different analyses.
Main Outcome Measures: CHD, CHD risk factors, and ANM.
Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in
women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were
found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging.
Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.</description><identifier>ISSN: 0021-972X</identifier><identifier>ISSN: 1945-7197</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgac171</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>The journal of clinical endocrinology and metabolism, 2022</ispartof><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,4024,26567,27923,27924,27925</link.rule.ids></links><search><creatorcontrib>Dam, Veerle</creatorcontrib><creatorcontrib>Onland-Moret, N. Charlotte</creatorcontrib><creatorcontrib>Burgess, Stephen</creatorcontrib><creatorcontrib>Chirlaque, Maria Dolores</creatorcontrib><creatorcontrib>Peters, Sanne A.E</creatorcontrib><creatorcontrib>Schuit, Ewoud</creatorcontrib><creatorcontrib>Tikk, Kaja</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Oliver-Williams, Clare</creatorcontrib><creatorcontrib>Wood, Angela M</creatorcontrib><creatorcontrib>Tjønneland, Anne</creatorcontrib><creatorcontrib>Dahm, Christina C</creatorcontrib><creatorcontrib>Overvad, Kim</creatorcontrib><creatorcontrib>Boutron-Rualt, Marie-Christine</creatorcontrib><creatorcontrib>Schulze, Matthias B</creatorcontrib><creatorcontrib>Trichopoulou, Antonia</creatorcontrib><creatorcontrib>Ferrari, Pietro</creatorcontrib><creatorcontrib>Masala, Giovanna</creatorcontrib><creatorcontrib>Krogh, Vittorio</creatorcontrib><creatorcontrib>Tumino, Rosario</creatorcontrib><creatorcontrib>Matullo, Giuseppe</creatorcontrib><creatorcontrib>Panico, Salvatore</creatorcontrib><creatorcontrib>Boer, Jolanda M. A</creatorcontrib><creatorcontrib>Verschuren, W.M. Monique</creatorcontrib><creatorcontrib>Waaseth, Marit</creatorcontrib><creatorcontrib>Pérez, María José Sánchez</creatorcontrib><creatorcontrib>Amiano, Pilar</creatorcontrib><creatorcontrib>Imaz, Liher</creatorcontrib><creatorcontrib>Moreno-Iribas, Conchi</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Harlid, Sophia</creatorcontrib><creatorcontrib>Nordendahl, Maria</creatorcontrib><creatorcontrib>Wennberg, Patrik</creatorcontrib><creatorcontrib>Key, Timothy J</creatorcontrib><creatorcontrib>Riboli, Elio</creatorcontrib><creatorcontrib>Santiuste, Carmen</creatorcontrib><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Katzke, Verena</creatorcontrib><creatorcontrib>Langenberg, Claudia</creatorcontrib><creatorcontrib>Wareham, Nicholas J</creatorcontrib><creatorcontrib>Schunkert, Heribert</creatorcontrib><creatorcontrib>Erdmann, Jeanette</creatorcontrib><creatorcontrib>Willenborg, Christina</creatorcontrib><creatorcontrib>Hengstenberg, Christian</creatorcontrib><creatorcontrib>Kleber, Marcus E</creatorcontrib><creatorcontrib>Delgado, Graciela</creatorcontrib><creatorcontrib>März, Winfried</creatorcontrib><creatorcontrib>Kanoni, Stavroula</creatorcontrib><creatorcontrib>Dedoussis, George</creatorcontrib><creatorcontrib>Deloukas, Panos</creatorcontrib><creatorcontrib>Nikpay, Majid</creatorcontrib><creatorcontrib>McPherson, Ruth</creatorcontrib><creatorcontrib>Scholz, Markus</creatorcontrib><creatorcontrib>Teren, Andrej</creatorcontrib><creatorcontrib>Butterworth, Adam S</creatorcontrib><creatorcontrib>van der Schouw, Yvonne T</creatorcontrib><title>Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization</title><title>The journal of clinical endocrinology and metabolism</title><description>Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart
disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.
Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk
factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men.
Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard
inverse-variance weighted (IVW) regression, and MR-Egger regression.
Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were
pooled for the different analyses.
Main Outcome Measures: CHD, CHD risk factors, and ANM.
Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in
women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were
found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging.
Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.</description><issn>0021-972X</issn><issn>1945-7197</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>3HK</sourceid><recordid>eNqFzLtOxDAQhWELgUS4tLTMC4T1OFms0CIuzTaIgi4a7CEMcuyVbS7L0xMkeqpTnE-_UmeoL9CgXrkgkeeVn8ihxT3V4NCvW4uD3VeN1gbbwZqnQ3VUypvW2PfrrlFfdxy5iqMQduC5cp6XiofM25z8u6vywUCTxAkoenApp0h5B69MuYKXwlT4CgiexUvmxS9_gPqZ2kLzNjBsOHoOQhEelkKa5Zt-0Yk6eKFQ-PRvj9X57c3j9X3rspQqcYwp04had3Y0l11vuv_FDzpjUuA</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Dam, Veerle</creator><creator>Onland-Moret, N. Charlotte</creator><creator>Burgess, Stephen</creator><creator>Chirlaque, Maria Dolores</creator><creator>Peters, Sanne A.E</creator><creator>Schuit, Ewoud</creator><creator>Tikk, Kaja</creator><creator>Weiderpass, Elisabete</creator><creator>Oliver-Williams, Clare</creator><creator>Wood, Angela M</creator><creator>Tjønneland, Anne</creator><creator>Dahm, Christina C</creator><creator>Overvad, Kim</creator><creator>Boutron-Rualt, Marie-Christine</creator><creator>Schulze, Matthias B</creator><creator>Trichopoulou, Antonia</creator><creator>Ferrari, Pietro</creator><creator>Masala, Giovanna</creator><creator>Krogh, Vittorio</creator><creator>Tumino, Rosario</creator><creator>Matullo, Giuseppe</creator><creator>Panico, Salvatore</creator><creator>Boer, Jolanda M. A</creator><creator>Verschuren, W.M. Monique</creator><creator>Waaseth, Marit</creator><creator>Pérez, María José Sánchez</creator><creator>Amiano, Pilar</creator><creator>Imaz, Liher</creator><creator>Moreno-Iribas, Conchi</creator><creator>Melander, Olle</creator><creator>Harlid, Sophia</creator><creator>Nordendahl, Maria</creator><creator>Wennberg, Patrik</creator><creator>Key, Timothy J</creator><creator>Riboli, Elio</creator><creator>Santiuste, Carmen</creator><creator>Kaaks, Rudolf</creator><creator>Katzke, Verena</creator><creator>Langenberg, Claudia</creator><creator>Wareham, Nicholas J</creator><creator>Schunkert, Heribert</creator><creator>Erdmann, Jeanette</creator><creator>Willenborg, Christina</creator><creator>Hengstenberg, Christian</creator><creator>Kleber, Marcus E</creator><creator>Delgado, Graciela</creator><creator>März, Winfried</creator><creator>Kanoni, Stavroula</creator><creator>Dedoussis, George</creator><creator>Deloukas, Panos</creator><creator>Nikpay, Majid</creator><creator>McPherson, Ruth</creator><creator>Scholz, Markus</creator><creator>Teren, Andrej</creator><creator>Butterworth, Adam S</creator><creator>van der Schouw, Yvonne T</creator><general>Oxford University Press</general><scope>3HK</scope></search><sort><creationdate>2022</creationdate><title>Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization</title><author>Dam, Veerle ; Onland-Moret, N. Charlotte ; Burgess, Stephen ; Chirlaque, Maria Dolores ; Peters, Sanne A.E ; Schuit, Ewoud ; Tikk, Kaja ; Weiderpass, Elisabete ; Oliver-Williams, Clare ; Wood, Angela M ; Tjønneland, Anne ; Dahm, Christina C ; Overvad, Kim ; Boutron-Rualt, Marie-Christine ; Schulze, Matthias B ; Trichopoulou, Antonia ; Ferrari, Pietro ; Masala, Giovanna ; Krogh, Vittorio ; Tumino, Rosario ; Matullo, Giuseppe ; Panico, Salvatore ; Boer, Jolanda M. A ; Verschuren, W.M. Monique ; Waaseth, Marit ; Pérez, María José Sánchez ; Amiano, Pilar ; Imaz, Liher ; Moreno-Iribas, Conchi ; Melander, Olle ; Harlid, Sophia ; Nordendahl, Maria ; Wennberg, Patrik ; Key, Timothy J ; Riboli, Elio ; Santiuste, Carmen ; Kaaks, Rudolf ; Katzke, Verena ; Langenberg, Claudia ; Wareham, Nicholas J ; Schunkert, Heribert ; Erdmann, Jeanette ; Willenborg, Christina ; Hengstenberg, Christian ; Kleber, Marcus E ; Delgado, Graciela ; März, Winfried ; Kanoni, Stavroula ; Dedoussis, George ; Deloukas, Panos ; Nikpay, Majid ; McPherson, Ruth ; Scholz, Markus ; Teren, Andrej ; Butterworth, Adam S ; van der Schouw, Yvonne T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-cristin_nora_10037_263423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dam, Veerle</creatorcontrib><creatorcontrib>Onland-Moret, N. 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A</creatorcontrib><creatorcontrib>Verschuren, W.M. Monique</creatorcontrib><creatorcontrib>Waaseth, Marit</creatorcontrib><creatorcontrib>Pérez, María José Sánchez</creatorcontrib><creatorcontrib>Amiano, Pilar</creatorcontrib><creatorcontrib>Imaz, Liher</creatorcontrib><creatorcontrib>Moreno-Iribas, Conchi</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Harlid, Sophia</creatorcontrib><creatorcontrib>Nordendahl, Maria</creatorcontrib><creatorcontrib>Wennberg, Patrik</creatorcontrib><creatorcontrib>Key, Timothy J</creatorcontrib><creatorcontrib>Riboli, Elio</creatorcontrib><creatorcontrib>Santiuste, Carmen</creatorcontrib><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Katzke, Verena</creatorcontrib><creatorcontrib>Langenberg, Claudia</creatorcontrib><creatorcontrib>Wareham, Nicholas J</creatorcontrib><creatorcontrib>Schunkert, Heribert</creatorcontrib><creatorcontrib>Erdmann, Jeanette</creatorcontrib><creatorcontrib>Willenborg, Christina</creatorcontrib><creatorcontrib>Hengstenberg, Christian</creatorcontrib><creatorcontrib>Kleber, Marcus E</creatorcontrib><creatorcontrib>Delgado, Graciela</creatorcontrib><creatorcontrib>März, Winfried</creatorcontrib><creatorcontrib>Kanoni, Stavroula</creatorcontrib><creatorcontrib>Dedoussis, George</creatorcontrib><creatorcontrib>Deloukas, Panos</creatorcontrib><creatorcontrib>Nikpay, Majid</creatorcontrib><creatorcontrib>McPherson, Ruth</creatorcontrib><creatorcontrib>Scholz, Markus</creatorcontrib><creatorcontrib>Teren, Andrej</creatorcontrib><creatorcontrib>Butterworth, Adam S</creatorcontrib><creatorcontrib>van der Schouw, Yvonne T</creatorcontrib><collection>NORA - Norwegian Open Research Archives</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dam, Veerle</au><au>Onland-Moret, N. Charlotte</au><au>Burgess, Stephen</au><au>Chirlaque, Maria Dolores</au><au>Peters, Sanne A.E</au><au>Schuit, Ewoud</au><au>Tikk, Kaja</au><au>Weiderpass, Elisabete</au><au>Oliver-Williams, Clare</au><au>Wood, Angela M</au><au>Tjønneland, Anne</au><au>Dahm, Christina C</au><au>Overvad, Kim</au><au>Boutron-Rualt, Marie-Christine</au><au>Schulze, Matthias B</au><au>Trichopoulou, Antonia</au><au>Ferrari, Pietro</au><au>Masala, Giovanna</au><au>Krogh, Vittorio</au><au>Tumino, Rosario</au><au>Matullo, Giuseppe</au><au>Panico, Salvatore</au><au>Boer, Jolanda M. A</au><au>Verschuren, W.M. Monique</au><au>Waaseth, Marit</au><au>Pérez, María José Sánchez</au><au>Amiano, Pilar</au><au>Imaz, Liher</au><au>Moreno-Iribas, Conchi</au><au>Melander, Olle</au><au>Harlid, Sophia</au><au>Nordendahl, Maria</au><au>Wennberg, Patrik</au><au>Key, Timothy J</au><au>Riboli, Elio</au><au>Santiuste, Carmen</au><au>Kaaks, Rudolf</au><au>Katzke, Verena</au><au>Langenberg, Claudia</au><au>Wareham, Nicholas J</au><au>Schunkert, Heribert</au><au>Erdmann, Jeanette</au><au>Willenborg, Christina</au><au>Hengstenberg, Christian</au><au>Kleber, Marcus E</au><au>Delgado, Graciela</au><au>März, Winfried</au><au>Kanoni, Stavroula</au><au>Dedoussis, George</au><au>Deloukas, Panos</au><au>Nikpay, Majid</au><au>McPherson, Ruth</au><au>Scholz, Markus</au><au>Teren, Andrej</au><au>Butterworth, Adam S</au><au>van der Schouw, Yvonne T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><date>2022</date><risdate>2022</risdate><issn>0021-972X</issn><issn>1945-7197</issn><eissn>1945-7197</eissn><abstract>Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart
disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause.
Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk
factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men.
Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard
inverse-variance weighted (IVW) regression, and MR-Egger regression.
Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were
pooled for the different analyses.
Main Outcome Measures: CHD, CHD risk factors, and ANM.
Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in
women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were
found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging.
Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.</abstract><pub>Oxford University Press</pub><doi>10.1210/clinem/dgac171</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2022 |
| issn | 0021-972X 1945-7197 1945-7197 |
| language | eng |
| recordid | cdi_cristin_nora_10037_26342 |
| source | NORA - Norwegian Open Research Archives; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| title | Genetically determined reproductive aging and coronary heart disease: a bidirectional two-sample Mendelian Randomization |
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