Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease-Findings from the Malmö Diet and Cancer Study
Fritz, Josef ; Shiffman, Dov ; Melander, Olle LU
; Tada, Hayato
and Ulmer, Hanno
(2017)
In Journal of the American Heart Association
6(3).
- Abstract
Background--Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Methods and Results--Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest... (More)
Background--Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Methods and Results--Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95% CI: 5.8-11.7%) by the apoB pathway, 1.7% (95% CI: 0.2-3.4%) by apoA-I, 8.5% (95% CI: 5.9-12.0%) by blood pressure, and 1.5% (95% CI: 0.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of GRS50 were mediated: 8.1% (95% CI: 5.5-11.8%) by apoB, 1.2% (95% CI: 0.5-3.0%) by apoA-I, 4.2% (95% CI: 1.3-7.5%) by blood pressure, and 0.9% (95% CI: 3.7% to 1.6%) by diabetes mellitus. Conclusions--A fraction of the CHD risk associated with family history or with GRS50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (≥80%) of the genetic effect operates independently of established metabolic risk factor pathways.
(Less)
- author
- Fritz, Josef
; Shiffman, Dov
; Melander, Olle
LU
; Tada, Hayato
and Ulmer, Hanno
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Coronary heart disease, Epidemiology, Family history, Genetic association, Risk factor
- in
- Journal of the American Heart Association
- volume
- 6
- issue
- 3
- article number
- e005254
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:28320750
- wos:000399322900046
- scopus:85032574622
- ISSN
- 2047-9980
- DOI
- 10.1161/JAHA.116.005254
- language
- English
- LU publication?
- yes
- id
- 143564bb-e849-4b48-a255-46430a7e469d
- date added to LUP
- 2017-11-08 10:02:23
- date last changed
- 2024-04-14 21:56:23
@article{143564bb-e849-4b48-a255-46430a7e469d,
abstract = {{<p>Background--Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Methods and Results--Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95% CI: 5.8-11.7%) by the apoB pathway, 1.7% (95% CI: 0.2-3.4%) by apoA-I, 8.5% (95% CI: 5.9-12.0%) by blood pressure, and 1.5% (95% CI: 0.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of GRS50 were mediated: 8.1% (95% CI: 5.5-11.8%) by apoB, 1.2% (95% CI: 0.5-3.0%) by apoA-I, 4.2% (95% CI: 1.3-7.5%) by blood pressure, and 0.9% (95% CI: 3.7% to 1.6%) by diabetes mellitus. Conclusions--A fraction of the CHD risk associated with family history or with GRS50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (≥80%) of the genetic effect operates independently of established metabolic risk factor pathways.</p>}},
author = {{Fritz, Josef and Shiffman, Dov and Melander, Olle and Tada, Hayato and Ulmer, Hanno}},
issn = {{2047-9980}},
keywords = {{Coronary heart disease; Epidemiology; Family history; Genetic association; Risk factor}},
language = {{eng}},
number = {{3}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of the American Heart Association}},
title = {{Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease-Findings from the Malmö Diet and Cancer Study}},
url = {{http://dx.doi.org/10.1161/JAHA.116.005254}},
doi = {{10.1161/JAHA.116.005254}},
volume = {{6}},
year = {{2017}},
}