Polygenic risk in Type III hyperlipidaemia and risk of cardiovascular disease : An epidemiological study in UK Biobank and Oxford Biobank
(2023) In International Journal of Cardiology 373. p.72-78- Abstract
Background: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL. Methods: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB. Results: One TG.PS standard-deviation... (More)
Background: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL. Methods: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB. Results: One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0–14.0%) greater TG in OBB and 15.2% (15.0–15.4%) in UKB. APOE22 carriers had 19.0% (1.0–39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0–6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3–1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; −0.35 (−0.29 to −0.40)g/L, UKB; −0.41 (−0.405 to −0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76–1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69–0.95); no differences were observed in CVD incidence. Conclusions: TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.
(Less)
- author
- Pieri, Kyriaki ; Trichia, Eirini ; Neville, Matt J. ; Taylor, Hannah ; Bennett, Derrick ; Karpe, Fredrik and Koivula, Robert W. LU
- organization
- publishing date
- 2023-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- APOE genotype, Cardiovascular disease, Dysbetalipoproteinaemia, NMR metabolomics, Polygenic risk, Type III hyperlipidaemia
- in
- International Journal of Cardiology
- volume
- 373
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:36410544
- scopus:85142773531
- ISSN
- 0167-5273
- DOI
- 10.1016/j.ijcard.2022.11.024
- language
- English
- LU publication?
- yes
- id
- 3dbcbbca-ef52-4d5b-bac5-2fe28784929c
- date added to LUP
- 2023-01-31 14:19:46
- date last changed
- 2024-04-15 19:50:35
@article{3dbcbbca-ef52-4d5b-bac5-2fe28784929c,
abstract = {{<p>Background: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL. Methods: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB. Results: One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0–14.0%) greater TG in OBB and 15.2% (15.0–15.4%) in UKB. APOE22 carriers had 19.0% (1.0–39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0–6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3–1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; −0.35 (−0.29 to −0.40)g/L, UKB; −0.41 (−0.405 to −0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76–1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69–0.95); no differences were observed in CVD incidence. Conclusions: TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.</p>}},
author = {{Pieri, Kyriaki and Trichia, Eirini and Neville, Matt J. and Taylor, Hannah and Bennett, Derrick and Karpe, Fredrik and Koivula, Robert W.}},
issn = {{0167-5273}},
keywords = {{APOE genotype; Cardiovascular disease; Dysbetalipoproteinaemia; NMR metabolomics; Polygenic risk; Type III hyperlipidaemia}},
language = {{eng}},
pages = {{72--78}},
publisher = {{Elsevier}},
series = {{International Journal of Cardiology}},
title = {{Polygenic risk in Type III hyperlipidaemia and risk of cardiovascular disease : An epidemiological study in UK Biobank and Oxford Biobank}},
url = {{http://dx.doi.org/10.1016/j.ijcard.2022.11.024}},
doi = {{10.1016/j.ijcard.2022.11.024}},
volume = {{373}},
year = {{2023}},
}