Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study

Jason Y.Y. Wong, Helene G Margolis, Mitchell Machiela, Weiyin Zhou, Michelle C. Odden, Bruce M. Psaty, John A Robbins, Rena R. Jones, Jerome I. Rotter, Stephen J. Chanock, Nathaniel Rothman, Qing Lan, Jennifer S. Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods: We analyzed baseline (1989–1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants’ monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results: Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m3), the middle (28.5–31.0 μg/m3; β = −0.0044, p = 0.09) and highest (≥31 μg/m3; β = −0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = −0.00035, p = 0.06) and smoking pack-years (β = −0.00011, p = 1.4E−3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions: PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalEnvironment International
Volume116
DOIs
StatePublished - Jul 1 2018

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chromosome
atmospheric pollution
smoking
particulate matter
mortality risk
nitrogen dioxide
mosaic
health
loss
sulfur dioxide
carbon monoxide
genomics
information system
blood
ozone
pollutant
air
exposure

Keywords

  • Air pollution
  • Genetic mosaicism
  • Genomic instability
  • Loss of chromosome Y
  • PM

ASJC Scopus subject areas

  • Environmental Science(all)

Cite this

Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study. / Wong, Jason Y.Y.; Margolis, Helene G; Machiela, Mitchell; Zhou, Weiyin; Odden, Michelle C.; Psaty, Bruce M.; Robbins, John A; Jones, Rena R.; Rotter, Jerome I.; Chanock, Stephen J.; Rothman, Nathaniel; Lan, Qing; Lee, Jennifer S.

In: Environment International, Vol. 116, 01.07.2018, p. 239-247.

Research output: Contribution to journalArticle

Wong, JYY, Margolis, HG, Machiela, M, Zhou, W, Odden, MC, Psaty, BM, Robbins, JA, Jones, RR, Rotter, JI, Chanock, SJ, Rothman, N, Lan, Q & Lee, JS 2018, 'Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study', Environment International, vol. 116, pp. 239-247. https://doi.org/10.1016/j.envint.2018.04.030
Wong, Jason Y.Y. ; Margolis, Helene G ; Machiela, Mitchell ; Zhou, Weiyin ; Odden, Michelle C. ; Psaty, Bruce M. ; Robbins, John A ; Jones, Rena R. ; Rotter, Jerome I. ; Chanock, Stephen J. ; Rothman, Nathaniel ; Lan, Qing ; Lee, Jennifer S. / Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study. In: Environment International. 2018 ; Vol. 116. pp. 239-247.
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abstract = "Background: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods: We analyzed baseline (1989–1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants’ monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results: Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m3), the middle (28.5–31.0 μg/m3; β = −0.0044, p = 0.09) and highest (≥31 μg/m3; β = −0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = −0.00035, p = 0.06) and smoking pack-years (β = −0.00011, p = 1.4E−3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions: PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.",
keywords = "Air pollution, Genetic mosaicism, Genomic instability, Loss of chromosome Y, PM",
author = "Wong, {Jason Y.Y.} and Margolis, {Helene G} and Mitchell Machiela and Weiyin Zhou and Odden, {Michelle C.} and Psaty, {Bruce M.} and Robbins, {John A} and Jones, {Rena R.} and Rotter, {Jerome I.} and Chanock, {Stephen J.} and Nathaniel Rothman and Qing Lan and Lee, {Jennifer S.}",
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AU - Margolis, Helene G

AU - Machiela, Mitchell

AU - Zhou, Weiyin

AU - Odden, Michelle C.

AU - Psaty, Bruce M.

AU - Robbins, John A

AU - Jones, Rena R.

AU - Rotter, Jerome I.

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Lan, Qing

AU - Lee, Jennifer S.

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N2 - Background: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods: We analyzed baseline (1989–1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants’ monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results: Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m3), the middle (28.5–31.0 μg/m3; β = −0.0044, p = 0.09) and highest (≥31 μg/m3; β = −0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = −0.00035, p = 0.06) and smoking pack-years (β = −0.00011, p = 1.4E−3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions: PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

AB - Background: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods: We analyzed baseline (1989–1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants’ monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results: Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m3), the middle (28.5–31.0 μg/m3; β = −0.0044, p = 0.09) and highest (≥31 μg/m3; β = −0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = −0.00035, p = 0.06) and smoking pack-years (β = −0.00011, p = 1.4E−3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions: PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

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KW - Loss of chromosome Y

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