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. 2024 Jun 5:471:134315.
doi: 10.1016/j.jhazmat.2024.134315. Epub 2024 Apr 16.

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study

Xin Guan  1 , Xia Meng  2 , Guorong Zhong  1 , Zirui Zhang  1 , Chenming Wang  1 , Yang Xiao  1 , Ming Fu  1 , Hui Zhao  1 , Yuhan Zhou  1 , Shiru Hong  1 , Xuedan Xu  1 , Yansen Bai  3 , Haidong Kan  2 , Renjie Chen  2 , Tangchun Wu  1 , Huan Guo  4
Affiliations

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study

Xin Guan et al. J Hazard Mater. .

Abstract

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [β (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.

Keywords: Male population; Mosaic loss of chromosome Y; PM(10); PM(2.5); Polygenic risk score.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no competing financial interest. Environmental implication Generally, males had higher incidence and mortality in non-sex-specific diseases than females, while mosaic loss of Y chromosome (mLOY) is the most frequently detected structural mosaic event. It is critical to illustrate the effects of environment and genes on mLOY. Since PM2.5 and PM10 exposure have become a pervasive global health threat, we estimated the combined effects of individual PM levels and genetic variants on mLOY. Our findings shed light on the risk factors of mLOY, which may be delivering interventions to modify the susceptibility to diverse diseases among males.

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