Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep;42(9):1198-1206.
doi: 10.1161/ATVBAHA.122.317664. Epub 2022 Jul 14.

Limited Effect of Y Chromosome Variation on Coronary Artery Disease and Mortality in UK Biobank-Brief Report

Paul R H J Timmers  1   2 , James F Wilson  1   2
Affiliations

Limited Effect of Y Chromosome Variation on Coronary Artery Disease and Mortality in UK Biobank-Brief Report

Paul R H J Timmers et al. Arterioscler Thromb Vasc Biol. 2022 Sep.

Abstract

Background: The effect of genetic variation in the male-specific region of the Y chromosome (MSY) on coronary artery disease and cardiovascular risk factors has been disputed. In this study, we systematically assessed the association of MSY genetic variation on these traits using a kin-cohort analysis of family disease history in the largest sample to date.

Methods: We tested 90 MSY haplogroups against coronary artery disease, hypertension, blood pressure, classical lipid levels, and all-cause mortality in up to 152 186 unrelated, genomically British individuals from UK Biobank. Unlike previous studies, we did not adjust for heritable lifestyle factors (to avoid collider bias) and instead adjusted for geographic variables and socioeconomic deprivation, given the link between MSY haplogroups and geography. For family history traits, subject MSY haplogroups were tested against father and mother disease as validation and negative control, respectively.

Results: Our models find little evidence for an effect of any MSY haplogroup on cardiovascular risk in participants. Parental models confirm these findings.

Conclusions: Kin-cohort analysis of the Y chromosome uniquely allows for discoveries in subjects to be validated using family history data. Despite our large sample size, improved models, and parental validation, there is little evidence to suggest cardiovascular risk in UK Biobank is influenced by genetic variation in MSY.

Keywords: blood pressure; chromosomes, human, Y; coronary artery disease; genetic variation; hypertension; mortality.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Examples of geographic structuring of Y chromosome variation by place of birth of genetically British men from UK Biobank. The prevalence of male-specific region of the Y chromosome haplogroups was plotted by place of birth in successively larger areas with at least 100 individuals, from wards and electoral divisions, to local authorities, to regions of England and the nations of Great Britain. Displayed are examples with pronounced structuring (A) I1-M253 (B) P-M45, (C) E1b1b-V13, (D) R1b-S749. Note the prevalence scales are different between haplogroups. See https://doi.org/10.7488/ds/3472 for maps of all 90 haplogroups.
Figure 2.
Figure 2.
Parental validation does not support putative male-specific region of the Y chromosome (MSY) haplogroup associations with subject coronary artery disease (CAD). Shown are the 6 MSY haplogroups showing some suggestive association with subject CAD (P<0.10) in models adjusted for socioeconomic and geographic variables (out of 66 haplogroups tested). Effect estimate units are log odds ratios for CAD (subjects) or heart disease (parents). Lines around point estimates represent 95% CIs. See Table S5 for all MSY haplogroups. OR indicates odds ratio.
See this image and copyright information in PMC

References

    1. Jobling MA, Tyler-Smith C. Human Y-chromosome variation in the genome-sequencing era. Nat Rev Genet. 2017;18:485–497. doi: 10.1038/nrg.2017.36 - PubMed
    1. Jobling MA, Tyler-Smith C. The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet. 2003;4:598–612. doi: 10.1038/nrg1124 - PubMed
    1. Foster EA, Jobling MA, Taylor PG, Donnelly P, de Knijff P, Mieremet R, Zerjal T, Tyler-Smith C. Jefferson fathered slave’s last child. Nature. 1998;396:27–28. doi: 10.1038/23835 - PubMed
    1. Capelli C, Redhead N, Abernethy JK, Gratrix F, Wilson JF, Moen T, Hervig T, Richards M, Stumpf MP, Underhill PA, et al. A Y chromosome census of the British Isles. Curr Biol. 2003;13:979–984. doi: 10.1016/s0960-9822(03)00373-7 - PubMed
    1. Ellis JA, Stebbing M, Harrap SB. Association of the human Y chromosome with high blood pressure in the general population. Hypertension. [Internet]. 2000;36:731–733. doi: 10.1161/01.hyp.36.5.731 - PubMed

Publication types