Cohort Profile: The Corogene study

Vaara, Satu; Nieminen, Markku S.; Lokki, Marja-Liisa; Perola, Markus; Pussinen, Pirkko J.; Allonen, Jaakko; Parkkonen, Olavi; Sinisalo, Juha

doi:10.1093/ije/dyr090

Cited by 54 publications

(61 citation statements)

References 17 publications

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“…Of the Corogene study, 2500 patients with acute coronary syndrome (International Classification of Diseases-Tenth Revision: I20-I25) were included in a genome-wide association study with a case-control setting. 29 Here, we used available genome-wide association data to test the association of rs77878271 with myocardial infarction (MI, International Classification of DiseasesTenth Revision, I21) using 1565 MI cases from the Corogene cohort and 1867 controls selected from the FINRISK surveys.…”

Section: The Corogene Studymentioning

confidence: 99%

“…We further explored the association of rs77878271 with MI in a large case-control data set, derived from the Corogene study, 29 with available genome-wide genotyping data using imputational approaches. In this data set, using a recessive model, the rs77878271 CC homozygotes showed 6-fold lower odds for MI (P=0.08; odds ratio, 0.17; 95% CI, 0.004-1.33; MI, n=1565; controls, n=1867; imputation info 0.97; minor allele frequency 5.9%; Hardy-Weinberg equilibrium from best guess genotypes P=0.90).…”

Section: Homozygote Carriers Of the Low-expression Variant Show Low Rmentioning

confidence: 99%

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Low-Expression Variant of Fatty Acid–Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability

Saksi

Ijäs

Mäyränpää

et al. 2014

Circ Cardiovasc Genet

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Background-Fatty acid-binding protein 4 (FABP4 or aP2 in mice) has been identified as a key regulator of core aspects of cardiometabolic disorders, including lipotoxic endoplasmic reticulum stress in macrophages. A functional promoter polymorphism (rs77878271) of human FABP4 gene has been described resulting in reduced FABP4 transcription. Methods and Results-We investigated the effects of this low-expression variant of FABP4 on cardiovascular morbidity and carotid atherosclerosis on a population level (n=7491) and in patient cohorts representing endarterectomized patients with advanced carotid atherosclerosis (n=92) and myocardial infarction (n=3432). We found that the low-expression variant was associated with decreased total cholesterol levels (P=0.006) with the largest reduction in variant allele homozygotes. Obese variant allele carriers also showed reduced carotid intima-media thickness (P=0.010) and lower prevalence of carotid plaques (P=0.060). Consistently, the variant allele homozygotes showed 8-fold lower odds for myocardial infarction (P=0.019; odds ratio, 0.12; 95% confidence interval, 0.003-0.801). Within the carotid plaques, the variant allele was associated with a 3.8-fold reduction in FABP4 transcription (P=0.049) and 2.7-fold reduction in apoptosis (activated caspase 3; P=0.043). Furthermore, the variant allele was enriched to patients with asymptomatic carotid stenosis (P=0.038). High FABP4 expression in the carotid plaques was associated with lipid accumulation, intraplaque hemorrhages, plaque ulcerations, and phosphoactivated endoplasmic reticulum stress markers. Conclusions-Our results reveal FABP4 rs77878271 as a novel variant affecting serum total cholesterol levels and cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the atherosclerotic plaque may promote lesion stability through modulation of endoplasmic reticulum stress signaling, and attenuation of apoptosis, lipid burden, and inflammation. (Circ Cardiovasc Genet. 2014;7:588-598.)

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Section: The Corogene Studymentioning

confidence: 99%

Section: Homozygote Carriers Of the Low-expression Variant Show Low Rmentioning

confidence: 99%

Low-Expression Variant of Fatty Acid–Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability

Saksi

Ijäs

Mäyränpää

et al. 2014

Circ Cardiovasc Genet

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“…The Corogene cohort is a case-control dataset including 2113 Finnish CHD patients and their matched controls [17]. CHD patients were collected from the Helsinki University Hospital in 2006-2008, where CHD was defined as coronary artery obstruction > 50% in at least one coronary artery.…”

Section: Individual-level Data Analysis Study Cohortsmentioning

confidence: 99%

Genetic support for the causal role of insulin in coronary heart disease

et al. 2016

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Aims/hypothesis Epidemiological studies have identified several traits associated with CHD, but few of these have been shown to be causal risk factors and thus suitable targets for treatment. Our aim was to evaluate the causal role of a large set of known CHD risk factors using single-nucleotide polymorphisms (SNPs) as instrumental variables. Methods Based on published genome-wide association studies (GWASs), we estimated the associations between the established risk factors (blood lipids, obesity, glycaemic traits and BP) and CHD with two complementary approaches: (1) using summary statistics from GWASs to analyse the accordance of SNP effects on risk factors and on CHD; and (2) individual-level analysis where we constructed genetic risk scores (GRSs) in a large Finnish dataset (N = 26,554, CHD events n = 4016).We used a weighted regression-based method for summary-level data to evaluate the causality of risk factors. The associations between the GRSs and CHD in the Finnish dataset were evaluated with logistic and conditional logistic regression models. Results The summary-level data analysis revealed causal effects between glycaemic traits (insulin and glucose) and CHD. The individual-level data analysis supported the causal role of insulin, but not of glucose, on CHD. The GRS for insulin was associated with CHD in the Finnish cohort (OR 1.06 per SD in GRS, 95% CI 1.02, 1.10, p = 0.002). Conclusions/interpretation These results support the causal role of insulin in the pathogenesis of CHD. Efficient treatment and prevention of insulin resistance is essential to prevent future CHD events.

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“…The cohort profile has been described earlier in detail (11). The Parogene study is a subsample of the COROGENE study.…”

Section: Subjects and Recruitment (I) Parogene 1 And 2 Populationsmentioning

confidence: 99%

Genetic Variation on the BAT1-NFKBIL1-LTA Region of Major Histocompatibility Complex Class III Associates with Periodontitis

et al. 2014

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Periodontitis is a chronic inflammatory disease with a multifactorial etiology. We investigated whether human major histocompatibility complex (MHC) polymorphisms (6p21.3) are associated with periodontal parameters. Parogene 1 population samples (n ‫؍‬ 169) were analyzed with 13,245 single nucleotide polymorphisms (SNPs) of the MHC region. Eighteen selected SNPs (P < 0.001) were replicated in Parogene 2 population samples (n ‫؍‬ 339) and the Health 2000 Survey (n ‫؍‬ 1,420). All subjects had a detailed clinical and radiographic oral health examination. Serum lymphotoxin-␣ (LTA) concentrations were measured in the Parogene populations, and the protein was detected in inflamed periodontal tissue. In the Parogene 1 population, 10 SNPs were associated with periodontal parameters. The strongest associations emerged from the parameters bleeding on probing (BOP) and a probing pocket depth (PPD) of >6 mm with the genes BAT1, NFKBIL1, and LTA. Six SNPs, rs11796, rs3130059, rs2239527, rs2071591, rs909253, and rs1041981 (r 2 , >0.92), constituted a risk haplotype. In the Parogene 1 population, the haplotype had the strongest association with the parameter BOP, a PPD of >6 mm, and severe periodontitis with odds ratios (95% confidence intervals) of 2.63 (2.21 to 3.20), 2.90 (2.37 to 3.52), and 3.10 (1.63 to 5.98), respectively. These results were replicated in the other two populations. High serum LTA concentrations in the Parogene population were associated with the periodontitis risk alleles of the LTA SNPs (rs909253 and rs1041981) of the haplotype. In addition, the protein was expressed in inflamed gingival connective tissue. We identified a novel BAT1-NFKBIL1-LTA haplotype as a significant contributor to the risk of periodontitis. The genetic polymorphisms in the MHC class III region may be functionally important in periodontitis susceptibility.

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Cohort Profile: The Corogene study

Cited by 54 publications

References 17 publications

Low-Expression Variant of Fatty Acid–Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability

Low-Expression Variant of Fatty Acid–Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability

Genetic support for the causal role of insulin in coronary heart disease

Genetic Variation on the BAT1-NFKBIL1-LTA Region of Major Histocompatibility Complex Class III Associates with Periodontitis

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