CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]

Publication Date:
2018-05-05
Publisher:
American Heart Association (AHA)
Print ISSN:
1942-325X
Electronic ISSN:
1942-3268
Topics:
Medicine
Keywords:
Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
Published by:
http://www.americanheart.org/
_version_ 1836398918174244864
autor Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
beschreibung Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants ( P 〈5 x 10 –8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (–0.23 mmol/L; 95% confidence interval, –0.26 to –0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
citation_standardnr 6251281
datenlieferant ipn_articles
feed_id 110195
feed_publisher American Heart Association (AHA)
feed_publisher_url http://www.americanheart.org/
insertion_date 2018-05-05
journaleissn 1942-3268
journalissn 1942-325X
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Heart Association (AHA)
quelle Circulation: Cardiovascular Genetics
relation http://circgenetics.ahajournals.org/cgi/content/short/11/5/e002034?rss=1
schlagwort Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
search_space articles
shingle_author_1 Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
shingle_author_2 Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
shingle_author_3 Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
shingle_author_4 Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
shingle_catch_all_1 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants ( P <5 x 10 –8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (–0.23 mmol/L; 95% confidence interval, –0.26 to –0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_2 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants ( P <5 x 10 –8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (–0.23 mmol/L; 95% confidence interval, –0.26 to –0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_3 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants ( P <5 x 10 –8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (–0.23 mmol/L; 95% confidence interval, –0.26 to –0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_4 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics
Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants ( P <5 x 10 –8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (–0.23 mmol/L; 95% confidence interval, –0.26 to –0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_title_1 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
shingle_title_2 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
shingle_title_3 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
shingle_title_4 CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
timestamp 2025-06-30T23:34:42.887Z
titel CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
titel_suche CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
topic WW-YZ
uid ipn_articles_6251281