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Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.
- Source :
-
International Journal of Epidemiology . Aug2017, Vol. 46 Issue 4, p1211-1222. 12p. - Publication Year :
- 2017
-
Abstract
- <bold>Background: </bold>Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.<bold>Methods: </bold>Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (ΔTC) and triglycerides (ΔTG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ∼ 190 000) and functional annotation for the top ranking variants.<bold>Results: </bold>In total, 956 variants were associated (P < 0.01) with either ΔTC or ΔTG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ΔTG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 × 10-8), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 × 10-6). The rs7412 variant at APOE was associated with ΔTC in GLACIER (P < 1.7 × 10-6). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ΔTC and for ΔTG, respectively (P < 10-3). Of these, a variant at CAPN3 (P = 1.2 × 10-4), multiple variants at HPR (Pmin = 1.5 × 10-6) and a variant at SIX5 (P = 1.9 × 10-4) showed evidence for association with CAD.<bold>Conclusions: </bold>We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03005771
- Volume :
- 46
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- International Journal of Epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 125319119
- Full Text :
- https://doi.org/10.1093/ije/dyw245