Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality

Abstract Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more ofte...

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Autores principales:	Angel Elenkov, Olle Melander, Peter M. Nilsson, He Zhang, Aleksander Giwercman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9d9594b173343ac99685f94649f6a28
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spelling	oai:doaj.org-article:d9d9594b173343ac99685f94649f6a282021-12-02T15:16:05ZImpact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality10.1038/s41598-021-97733-22045-2322https://doaj.org/article/d9d9594b173343ac99685f94649f6a282021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97733-2https://doaj.org/toc/2045-2322Abstract Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10–3.36) for GRS 50 and 1.54 (0.87–2.75) for GRS 27 in fathers to 3.12 (1.39–7.04) for GRS50 and 3.73 (1.75–7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84–0.92) and 0.86 (95% CI 0.84–0.90), and, AUC 0.81 (95% CI 0.75–0.87) and 0.78 (95% CI 0.73–0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.Angel ElenkovOlle MelanderPeter M. NilssonHe ZhangAleksander GiwercmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angel Elenkov Olle Melander Peter M. Nilsson He Zhang Aleksander Giwercman Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
description	Abstract Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10–3.36) for GRS 50 and 1.54 (0.87–2.75) for GRS 27 in fathers to 3.12 (1.39–7.04) for GRS50 and 3.73 (1.75–7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84–0.92) and 0.86 (95% CI 0.84–0.90), and, AUC 0.81 (95% CI 0.75–0.87) and 0.78 (95% CI 0.73–0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.
format	article
author	Angel Elenkov Olle Melander Peter M. Nilsson He Zhang Aleksander Giwercman
author_facet	Angel Elenkov Olle Melander Peter M. Nilsson He Zhang Aleksander Giwercman
author_sort	Angel Elenkov
title	Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
title_short	Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
title_full	Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
title_fullStr	Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
title_full_unstemmed	Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
title_sort	impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9d9594b173343ac99685f94649f6a28
work_keys_str_mv	AT angelelenkov impactofgeneticriskscoreontheassociationbetweenmalechildlessnessandcardiovasculardiseaseandmortality AT ollemelander impactofgeneticriskscoreontheassociationbetweenmalechildlessnessandcardiovasculardiseaseandmortality AT petermnilsson impactofgeneticriskscoreontheassociationbetweenmalechildlessnessandcardiovasculardiseaseandmortality AT hezhang impactofgeneticriskscoreontheassociationbetweenmalechildlessnessandcardiovasculardiseaseandmortality AT aleksandergiwercman impactofgeneticriskscoreontheassociationbetweenmalechildlessnessandcardiovasculardiseaseandmortality
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Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality

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