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

Elenkov, Angel LU ; Melander, Olle LU orcid ; Nilsson, Peter M LU ; Zhang, He LU and Giwercman, Aleksander LU (2021) In Scientific Reports 11. p.1-10
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... (More)
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. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
article number
18526
pages
1 - 10
publisher
Nature Publishing Group
external identifiers
  • scopus:85115382414
  • pmid:34535694
ISSN
2045-2322
DOI
10.1038/s41598-021-97733-2
project
AIR Lund - Artificially Intelligent use of Registers
MOVING FROM BIOMARKERS TO MECHANISM ORIENTED PREVENTION OF CARDIOMETABOLIC DISEASE
language
English
LU publication?
yes
id
b5039524-abe5-492b-8d04-4fc6e040d6db
date added to LUP
2021-11-10 12:54:32
date last changed
2024-01-05 18:54:39
@article{b5039524-abe5-492b-8d04-4fc6e040d6db,
  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.}},
  author       = {{Elenkov, Angel and Melander, Olle and Nilsson, Peter M and Zhang, He and Giwercman, Aleksander}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  pages        = {{1--10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-97733-2}},
  doi          = {{10.1038/s41598-021-97733-2}},
  volume       = {{11}},
  year         = {{2021}},
}