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Polygenic scores for low lung function and the future risk of adverse health outcomes

Zaigham, Suneela LU ; Gonçalves, Isabel LU orcid ; Engström, Gunnar LU and Sun, Jiangming LU orcid (2022) In Cardiovascular Diabetology 21(1). p.1-10
Abstract

AIMS: Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes.

METHODS: We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV
1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS.
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AIMS: Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes.

METHODS: We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV
1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS.

RESULTS: FEV
1-PGS and FVC-PGS were significantly associated with mean sBP at baseline after adjustments (FEV
1-PGS Q1 (highest PGS = highest lung function): 140.7mmHg vs. Q4: 141.5mmHg, p-value 0.008). A low FVC-PGS was significantly associated with the risk of future diabetic events after adjustments (Q4 vs. Q1 HR: 1.22 (CI 1.12-1.32), p-trend < 0.001) and had added value to risk prediction models for diabetes. Low FEV
1-PGS was significantly associated with future coronary events (Q4 vs. Q1 HR: 1.13 (CI: 1.04-1.22), p-trend 0.008). No significant association was found between PGS and sudden cardiac death, chronic kidney disease or all-cause mortality. Results remained largely unchanged in a subgroup of subjects when further adjusted for apolipoproteins.

CONCLUSION: Genetic susceptibility for reduced lung function is associated with higher sBP, increased risk of diabetes and to a lesser extent, future coronary events, suggesting etiological roles of lung function on these outcomes. Using PGS, high-risk groups could be early detected to implement early lifestyle changes to mitigate the risk.

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Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Genetic susceptibility, Lung function, Coronary artery disease, Polygenic risk score, Diabetes, Early screening
in
Cardiovascular Diabetology
volume
21
issue
1
article number
230
pages
1 - 10
publisher
BioMed Central (BMC)
external identifiers
  • pmid:36329522
  • scopus:85141187171
ISSN
1475-2840
DOI
10.1186/s12933-022-01661-y
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
5421e43a-c829-4d52-ba30-6a0a8e2d21d8
date added to LUP
2022-11-11 17:01:44
date last changed
2025-04-19 04:18:27
@article{5421e43a-c829-4d52-ba30-6a0a8e2d21d8,
  abstract     = {{<p>AIMS: Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes.</p><p>METHODS: We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV<br>
 1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS.<br>
 </p><p>RESULTS: FEV<br>
 1-PGS and FVC-PGS were significantly associated with mean sBP at baseline after adjustments (FEV<br>
 1-PGS Q1 (highest PGS = highest lung function): 140.7mmHg vs. Q4: 141.5mmHg, p-value 0.008). A low FVC-PGS was significantly associated with the risk of future diabetic events after adjustments (Q4 vs. Q1 HR: 1.22 (CI 1.12-1.32), p-trend &lt; 0.001) and had added value to risk prediction models for diabetes. Low FEV <br>
 1-PGS was significantly associated with future coronary events (Q4 vs. Q1 HR: 1.13 (CI: 1.04-1.22), p-trend 0.008). No significant association was found between PGS and sudden cardiac death, chronic kidney disease or all-cause mortality. Results remained largely unchanged in a subgroup of subjects when further adjusted for apolipoproteins.<br>
 </p><p>CONCLUSION: Genetic susceptibility for reduced lung function is associated with higher sBP, increased risk of diabetes and to a lesser extent, future coronary events, suggesting etiological roles of lung function on these outcomes. Using PGS, high-risk groups could be early detected to implement early lifestyle changes to mitigate the risk.</p>}},
  author       = {{Zaigham, Suneela and Gonçalves, Isabel and Engström, Gunnar and Sun, Jiangming}},
  issn         = {{1475-2840}},
  keywords     = {{Genetic susceptibility; Lung function; Coronary artery disease; Polygenic risk score; Diabetes; Early screening}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{1}},
  pages        = {{1--10}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Cardiovascular Diabetology}},
  title        = {{Polygenic scores for low lung function and the future risk of adverse health outcomes}},
  url          = {{http://dx.doi.org/10.1186/s12933-022-01661-y}},
  doi          = {{10.1186/s12933-022-01661-y}},
  volume       = {{21}},
  year         = {{2022}},
}