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Genetically determined reproductive aging and coronary heart disease: a bidirectional 2-sample mendelian randomization

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.To study the direction and evidence for causality...

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Main Authors: Dam, Veerle (Author) , Onland-Moret, N Charlotte (Author) , Burgess, Stephen (Author) , Chirlaque, Maria-Dolores (Author) , Peters, Sanne A E (Author) , Schuit, Ewoud (Author) , Tikk, Kaja (Author) , Weiderpass, Elisabete (Author) , Oliver-Williams, Clare (Author) , Wood, Angela M (Author) , Tjønneland, Anne (Author) , Dahm, Christina C (Author) , Overvad, Kim (Author) , Boutron-Ruault, Marie-Christine (Author) , Schulze, Matthias B (Author) , Trichopoulou, Antonia (Author) , Ferrari, Pietro (Author) , Masala, Giovanna (Author) , Krogh, Vittorio (Author) , Tumino, Rosario (Author) , Matullo, Giuseppe (Author) , Panico, Salvatore (Author) , Boer, Jolanda M A (Author) , Verschuren, W M Monique (Author) , Waaseth, Marit (Author) , Pérez, Maria José Sánchez (Author) , Amiano, Pilar (Author) , Imaz, Liher (Author) , Moreno-Iribas, Conchi (Author) , Melander, Olle (Author) , Harlid, Sophia (Author) , Nordendahl, Maria (Author) , Wennberg, Patrik (Author) , Key, Timothy J (Author) , Riboli, Elio (Author) , Santiuste, Carmen (Author) , Kaaks, Rudolf (Author) , Katzke, Verena (Author) , Langenberg, Claudia (Author) , Wareham, Nicholas J (Author) , Schunkert, Heribert (Author) , Erdmann, Jeanette (Author) , Willenborg, Christina (Author) , Hengstenberg, Christian (Author) , Kleber, Marcus E. (Author) , Delgado Gonzales de Kleber, Graciela (Author) , März, Winfried (Author) , Kanoni, Stavroula (Author) , Dedoussis, George (Author) , Deloukas, Panos (Author) , Nikpay, Majid (Author) , McPherson, Ruth (Author) , Scholz, Markus (Author) , Teren, Andrej (Author) , Butterworth, Adam S (Author) , van der Schouw, Yvonne T (Author)
Format: Article (Journal)
Language:English
Published: 20 March 2022
In: The journal of clinical endocrinology & metabolism
Year: 2022, Volume: 107, Issue: 7, Pages: e2952-e2961
ISSN:1945-7197
DOI:10.1210/clinem/dgac171
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1210/clinem/dgac171
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/jcem/article/107/7/e2952/6550950?login=true
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Author Notes:Veerle Dam, N. Charlotte Onland-Moret, Stephen Burgess, Maria-Dolores Chirlaque, Sanne A.E. Peters, Ewoud Schuit, Kaja Tikk, Elisabete Weiderpass, Clare Oliver-Williams, Angela M. Wood, Anne Tjønneland, Christina C. Dahm, Kim Overvad, Marie-Christine Boutron-Ruault, Matthias B. Schulze, Antonia Trichopoulou, Pietro Ferrari, Giovanna Masala, Vittorio Krogh, Rosario Tumino, Giuseppe Matullo, Salvatore Panico, Jolanda M.A. Boer, W.M. Monique Verschuren, Marit Waaseth, Maria José Sánchez Pérez, Pilar Amiano, Liher Imaz, Conchi Moreno-Iribas, Olle Melander, Sophia Harlid, Maria Nordendahl, Patrik Wennberg, Timothy J Key, Elio Riboli, Carmen Santiuste, Rudolf Kaaks, Verena Katzke, Claudia Langenberg, Nicholas J. Wareham, Heribert Schunkert, Jeanette Erdmann, Christina Willenborg, Christian Hengstenberg, Marcus E. Kleber, Graciela Delgado, Winfried März, Stavroula Kanoni, George Dedoussis, Panos Deloukas, Majid Nikpay, Ruth McPherson, Markus Scholz, Andrej Teren, Adam S. Butterworth, Yvonne T. van der Schouw
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Summary: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.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.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.Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses.CHD, CHD risk factors, and ANM.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.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.
Item Description:Gesehen am 09.01.2024
Physical Description:Online Resource
ISSN:1945-7197
DOI:10.1210/clinem/dgac171

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