Dataset Information

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

ABSTRACT: 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.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 (?TC) and triglycerides (?TG). 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.In total, 956 variants were associated (P < 0.01) with either ?TC or ?TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ?TG 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 ?TC in GLACIER (P < 1.7 × 10-6). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ?TC and for ?TG, 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.We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

SUBMITTER: Varga TV

PROVIDER: S-EPMC5837581 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Varga Tibor V TV Kurbasic Azra A Aine Mattias M Eriksson Pontus P Ali Ashfaq A Hindy George G Gustafsson Stefan S Luan Jian'an J Shungin Dmitry D Chen Yan Y Schulz Christina-Alexandra CA Nilsson Peter M PM Hallmans Göran G Barroso Inês I Deloukas Panos P Langenberg Claudia C Scott Robert A RA Wareham Nicholas J NJ Lind Lars L Ingelsson Erik E Melander Olle O Orho-Melander Marju M Renström Frida F Franks Paul W PW

International journal of epidemiology 20170801 4

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27864399

Similar Datasets

Project description:ImportanceThe level of coronary artery calcium (CAC) can effectively stratify cardiovascular risk in middle-aged and older adults, but its utility for young adults is unclear.ObjectivesTo determine the prevalence of CAC in adults aged 30 to 49 years and the subsequent association of CAC with coronary heart disease (CHD), cardiovascular disease (CVD), and all-cause mortality.Design, setting, and participantsA multicenter retrospective cohort study was conducted among 22 346 individuals from the CAC Consortium who underwent CAC testing (baseline examination, 1991-2010, with follow-up through June 30, 2014; CAC quantified using nonconrast, cardiac-gated computed tomography scans) for clinical indications and were followed up for cause-specific mortality. Participants were free of clinical CVD at baseline. Statistical analysis was performed from June 1, 2017, to May 31, 2018.Main outcomes and measuresThe prevalence of CAC and the subsequent rates of CHD, CVD, and all-cause mortality. Competing risks regression modeling was used to calculate multivariable-adjusted subdistribution hazard ratios for CHD and CVD mortality.ResultsThe sample of 22 346 participants (25.0% women and 75.0% men; mean [SD] age, 43.5 [4.5] years) had a high prevalence of hyperlipidemia (49.6%) and family history of CHD (49.3%) but a low prevalence of current smoking (11.0%) and diabetes (3.9%). The prevalence of any CAC was 34.4%, with 7.2% having a CAC score of more than 100. During follow-up (mean [SD], 12.7 [4.0] years), there were 40 deaths related to CHD, 84 deaths related to CVD, and 298 total deaths. A total of 27 deaths related to CHD (67.5%) occurred among individuals with CAC at baseline. The CHD mortality rate per 1000 person-years was 10-fold higher among those with a CAC score of more than 100 (0.69; 95% CI, 0.41-1.16) compared with those with a CAC score of 0 (0.07; 95% CI, 0.04-0.12). After multivariable adjustment, those with a CAC score of more than 100 had a significantly increased risk of CHD (subdistribution hazard ratio, 5.6; 95% CI, 2.5-12.7), CVD (subdistribution hazard ratio, 3.3; 95% CI, 1.8-6.2), and all-cause mortality (hazard ratio, 2.6; 95% CI, 1.9-3.6) compared with those with a CAC score of 0.Conclusions and relevanceIn a large sample of young adults undergoing CAC testing for clinical indications, 34.4% had CAC, and those with elevated CAC scores had significantly higher rates of CHD and CVD mortality. Coronary artery calcium may have potential utility for clinical decision-making among select young adults at elevated risk of cardiovascular disease.

Dataset Information

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Publications

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets