Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery

Eun Jeong Cheon, Do Hyeon Cha, Sung Kweon Cho, Hye Min Noh, Sungha Park, Seok Min Kang, Heon Yung Gee, Sang Hak Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and aims: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. Methods: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. Results: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. Conclusions: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalAtherosclerosis
Volume273
DOIs
Publication statusPublished - 2018 Jun

Fingerprint

Genome-Wide Association Study
Cholesterol
HDL Lipoproteins
HDL Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Genetic Models
Apolipoproteins B
Radioisotopes
LDL Cholesterol
Coronary Artery Disease
Linear Models
Triglycerides
Body Mass Index
Alcohols
Genome

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Cheon, Eun Jeong ; Cha, Do Hyeon ; Cho, Sung Kweon ; Noh, Hye Min ; Park, Sungha ; Kang, Seok Min ; Gee, Heon Yung ; Lee, Sang Hak. / Novel association between CDKAL1 and cholesterol efflux capacity : Replication after GWAS-based discovery. In: Atherosclerosis. 2018 ; Vol. 273. pp. 21-27.
@article{123af25da6b3453eac501bdf1480039f,
title = "Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery",
abstract = "Background and aims: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. Methods: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. Results: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. Conclusions: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.",
author = "Cheon, {Eun Jeong} and Cha, {Do Hyeon} and Cho, {Sung Kweon} and Noh, {Hye Min} and Sungha Park and Kang, {Seok Min} and Gee, {Heon Yung} and Lee, {Sang Hak}",
year = "2018",
month = "6",
doi = "10.1016/j.atherosclerosis.2018.04.011",
language = "English",
volume = "273",
pages = "21--27",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",

}

Novel association between CDKAL1 and cholesterol efflux capacity : Replication after GWAS-based discovery. / Cheon, Eun Jeong; Cha, Do Hyeon; Cho, Sung Kweon; Noh, Hye Min; Park, Sungha; Kang, Seok Min; Gee, Heon Yung; Lee, Sang Hak.

In: Atherosclerosis, Vol. 273, 06.2018, p. 21-27.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel association between CDKAL1 and cholesterol efflux capacity

T2 - Replication after GWAS-based discovery

AU - Cheon, Eun Jeong

AU - Cha, Do Hyeon

AU - Cho, Sung Kweon

AU - Noh, Hye Min

AU - Park, Sungha

AU - Kang, Seok Min

AU - Gee, Heon Yung

AU - Lee, Sang Hak

PY - 2018/6

Y1 - 2018/6

N2 - Background and aims: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. Methods: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. Results: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. Conclusions: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.

AB - Background and aims: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. Methods: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. Results: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. Conclusions: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.

UR - http://www.scopus.com/inward/record.url?scp=85045431248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045431248&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2018.04.011

DO - 10.1016/j.atherosclerosis.2018.04.011

M3 - Article

C2 - 29674289

AN - SCOPUS:85045431248

VL - 273

SP - 21

EP - 27

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -