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Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication.
Circ Cardiovasc Genet. 2008 Oct; 1(1):21-30.CC

Abstract

BACKGROUND

Genome-wide genetic association analysis represents an opportunity for a comprehensive survey of the genes governing lipid metabolism, potentially revealing new insights or even therapeutic strategies for cardiovascular disease and related metabolic disorders.

METHODS AND RESULTS

We have performed large-scale, genome-wide genetic analysis among 6382 white women with replication in 2 cohorts of 970 additional white men and women for associations between common single-nucleotide polymorphisms and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein(Apo) A1, and ApoB. Genome-wide associations (P < 5 x 10(-8)) were found at the PCSK9 gene, the APOB gene, theLPL gene, the APOA1-APOA5 locus, the LIPC gene, the CETP gene, the LDLR gene, and the APOE locus. In addition,genome-wide associations with triglycerides at the GCKR gene confirm and extend emerging links between glucose and lipid metabolism. Still other genome-wide associations at the 1p13.3 locus are consistent with emerging biological properties for a region of the genome, possibly related to the SORT1 gene. Below genome-wide significance, our study provides confirmatory evidence for associations at 5 novel loci with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides reported recently in separate genome-wide association studies. The total proportion of variance explained by common variation at the genome-wide candidate loci ranges from 4.3% for triglycerides to 12.6% for ApoB.

CONCLUSION

Genome-wide associations at the GCKR gene and near the SORT1 gene, as well as confirmatory associations at 5 additional novel loci, suggest emerging biological pathways for lipid metabolism among white women.

Authors+Show Affiliations

Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. dchasman@rics.bwh.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19802338

Citation

Chasman, Daniel I., et al. "Genetic Loci Associated With Plasma Concentration of Low-density Lipoprotein Cholesterol, High-density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-wide Analysis With Replication." Circulation. Cardiovascular Genetics, vol. 1, no. 1, 2008, pp. 21-30.
Chasman DI, Paré G, Zee RY, et al. Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication. Circ Cardiovasc Genet. 2008;1(1):21-30.
Chasman, D. I., Paré, G., Zee, R. Y., Parker, A. N., Cook, N. R., Buring, J. E., Kwiatkowski, D. J., Rose, L. M., Smith, J. D., Williams, P. T., Rieder, M. J., Rotter, J. I., Nickerson, D. A., Krauss, R. M., Miletich, J. P., & Ridker, P. M. (2008). Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication. Circulation. Cardiovascular Genetics, 1(1), 21-30. https://doi.org/10.1161/CIRCGENETICS.108.773168
Chasman DI, et al. Genetic Loci Associated With Plasma Concentration of Low-density Lipoprotein Cholesterol, High-density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-wide Analysis With Replication. Circ Cardiovasc Genet. 2008;1(1):21-30. PubMed PMID: 19802338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication. AU - Chasman,Daniel I, AU - Paré,Guillaume, AU - Zee,Robert Y L, AU - Parker,Alex N, AU - Cook,Nancy R, AU - Buring,Julie E, AU - Kwiatkowski,David J, AU - Rose,Lynda M, AU - Smith,Joshua D, AU - Williams,Paul T, AU - Rieder,Mark J, AU - Rotter,Jerome I, AU - Nickerson,Deborah A, AU - Krauss,Ronald M, AU - Miletich,Joseph P, AU - Ridker,Paul M, PY - 2009/10/6/entrez PY - 2009/10/6/pubmed PY - 2010/3/3/medline KW - GWAS KW - cardiovascular disease KW - lipid KW - lipoprotein SP - 21 EP - 30 JF - Circulation. Cardiovascular genetics JO - Circ Cardiovasc Genet VL - 1 IS - 1 N2 - BACKGROUND: Genome-wide genetic association analysis represents an opportunity for a comprehensive survey of the genes governing lipid metabolism, potentially revealing new insights or even therapeutic strategies for cardiovascular disease and related metabolic disorders. METHODS AND RESULTS: We have performed large-scale, genome-wide genetic analysis among 6382 white women with replication in 2 cohorts of 970 additional white men and women for associations between common single-nucleotide polymorphisms and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein(Apo) A1, and ApoB. Genome-wide associations (P < 5 x 10(-8)) were found at the PCSK9 gene, the APOB gene, theLPL gene, the APOA1-APOA5 locus, the LIPC gene, the CETP gene, the LDLR gene, and the APOE locus. In addition,genome-wide associations with triglycerides at the GCKR gene confirm and extend emerging links between glucose and lipid metabolism. Still other genome-wide associations at the 1p13.3 locus are consistent with emerging biological properties for a region of the genome, possibly related to the SORT1 gene. Below genome-wide significance, our study provides confirmatory evidence for associations at 5 novel loci with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides reported recently in separate genome-wide association studies. The total proportion of variance explained by common variation at the genome-wide candidate loci ranges from 4.3% for triglycerides to 12.6% for ApoB. CONCLUSION: Genome-wide associations at the GCKR gene and near the SORT1 gene, as well as confirmatory associations at 5 additional novel loci, suggest emerging biological pathways for lipid metabolism among white women. SN - 1942-3268 UR - https://www.unboundmedicine.com/medline/citation/19802338/Genetic_loci_associated_with_plasma_concentration_of_low_density_lipoprotein_cholesterol_high_density_lipoprotein_cholesterol_triglycerides_apolipoprotein_A1_and_Apolipoprotein_B_among_6382_white_women_in_genome_wide_analysis_with_replication_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCGENETICS.108.773168?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -