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ABSTRACT: Background. Sudden cardiac death (SCD) remains a major cause of death in Western countries. It has a heritable component, but previous molecular studies have mainly focused on common genetic variants. We studied the prevalence, clinical phenotypes, and risk of SCD presented by ten rare mutations previously associated with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, or catecholaminergic polymorphic ventricular tachycardia. Methods. The occurrence of ten arrhythmia-associated mutations was determined in four large prospective population cohorts (FINRISK 1992, 1997, 2002, and Health 2000, n = 28,465) and two series of forensic autopsies (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 825). Follow-up data were collected from national registries. Results. The ten mutations showed a combined prevalence of 79 per 10,000 individuals in Finland, and six of them showed remarkable geographic clustering. Of a total of 715 SCD cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W. Conclusions. Arrhythmia-associated mutations are prevalent in the general Finnish population but do not seem to present a major risk factor for SCD, at least during a mean of 10-year follow-up of a random adult population sample.
Annals of medicine 05/2013; · 3.52 Impact Factor
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Sonja I Berndt,
Stefan Gustafsson,
Reedik Mägi,
Andrea Ganna,
Eleanor Wheeler,
Mary F Feitosa,
Anne E Justice,
Keri L Monda,
Damien C Croteau-Chonka,
Felix R Day, [......],
Joel N Hirschhorn,
Cecilia M Lindgren,
Andrew P Morris,
David Meyre,
André Scherag,
Mark I McCarthy,
Elizabeth K Speliotes,
Kari E North,
Ruth J F Loos,
Erik Ingelsson
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ABSTRACT: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
Nature Genetics 04/2013; · 35.53 Impact Factor
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Sonja I Berndt,
Stefan Gustafsson,
Reedik Magi,
Andrea Ganna,
Eleanor Wheeler,
Mary F Feitosa,
Anne E Justice,
Keri L Monda,
Damien C Croteau-Chonka,
Felix R Day, [......],
Joel N Hirschhorn,
Cecilia M Lindgren,
Andrew P Morris,
David Meyre,
Andre Scherag,
Mark I McCarthy,
Elizabeth K Speliotes,
Kari E North,
Ruth J F Loos,
Erik Ingelsson
[show abstract]
[hide abstract]
ABSTRACT: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
Nature Genetics 04/2013; · 35.53 Impact Factor
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Marian Beekman,
Hélène Blanché, Markus Perola,
Anti Hervonen,
Vladyslav Bezrukov,
Ewa Sikora,
Frederieke Flachsbart,
Lene Christiansen,
Anton J M De Craen,
Thomas B L Kirkwood, [......],
Stefan Schreiber,
Mark Lathrop,
Axel Skytthe,
Rudi G J Westendorp,
Kaare Christensen,
Jutta Gampe,
Almut Nebel,
Jeanine J Houwing-Duistermaat,
P Eline Slagboom,
Claudio Franceschi
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Marian Beekman,
Hélène Blanché, Markus Perola,
Anti Hervonen,
Vladyslav Bezrukov,
Ewa Sikora,
Frederieke Flachsbart,
Lene Christiansen,
Anton J M De Craen,
Thomas B L Kirkwood, [......],
Stefan Schreiber,
Mark Lathrop,
Axel Skytthe,
Rudi G J Westendorp,
Kaare Christensen,
Jutta Gampe,
Almut Nebel,
Jeanine J Houwing-Duistermaat,
P Eline Slagboom,
Claudio Franceschi
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ABSTRACT: Cardiovascular risk factors increase the risk of dementia in later life. The aims of the current study were to assess the effect of multiple midlife cardiovascular risk factors on the risk of cognitive impairment in later life, and to assess the validity of the previously suggested CAIDE Study risk score predicting dementia risk 20 years later. A total of 2,165 Finnish twins were followed and at the end of the follow-up their cognitive status was assessed with a validated telephone interview. The assessment of the risk factors at baseline was based on a self-report questionnaire. Relative risk ratios (RR) were calculated and receiver operating characteristic analyses performed. Midlife obesity (RR 2.42, 95 % CI 1.47-3.98), hypertension (RR 1.38, 95 % CI 1.01-1.88) and low leisure time physical activity (RR 2.52, 95 % CI 1.10-5.76) increased the risk of cognitive impairment after a mean follow-up of 22.6 ± 2.3 years. Hypercholesterolemia did not significantly increase the risk (RR 1.52, 95 % CI 0.92-2.51). Overweight individuals who gained more than 10 % weight between 1981 and 1990 had an increased risk of cognitive impairment (RR 4.27, 95 % CI 1.62-11.2). The CAIDE Study risk score combining various individual risk factors had an area-under-curve of 0.74 (95 % CI 0.69-0.79, n = 591), and there was a strong association between an increasing risk score and the risk of cognitive impairment. The results indicate that multiple midlife cardiovascular risk factors increase the risk of cognitive impairment in later life. Also, a risk score including easily measurable midlife factors predicts an individual's cognitive impairment risk well.
European Journal of Epidemiology 03/2013; · 4.71 Impact Factor
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Veryan Codd,
Christopher P Nelson,
Eva Albrecht,
Massimo Mangino,
Joris Deelen,
Jessica L Buxton,
Jouke Jan Hottenga,
Krista Fischer,
Tõnu Esko,
Ida Surakka, [......],
Iiris Hovatta,
Christian Gieger,
Andres Metspalu,
Dorret I Boomsma,
Marjo-Riitta Jarvelin,
P Eline Slagboom,
John R Thompson,
Tim D Spector,
Pim van der Harst,
Nilesh J Samani
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ABSTRACT: Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
Nature Genetics 03/2013; 45(4):422-427. · 35.53 Impact Factor
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Jussi P Posti,
Perttu Salo,
Saku Ruohonen,
Laura Valve,
Mordechai Muszkat,
Gbenga G Sofowora,
Daniel Kurnik,
Charles Michael Stein, Markus Perola,
Mika Scheinin,
Amir Snapir
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ABSTRACT: OBJECTIVES: α2-Adrenoceptors (α2-AR) mediate both constriction and dilatation of blood vessels. There is considerable interindividual variability in dorsal hand vein (DHV) constriction responses to α2-AR agonist activation. Genetic factors appear to contribute significantly to this variation. The present study was designed to identify the genetic factors contributing toward the interindividual variability in α2-AR-mediated vascular constriction induced by the selective α2-AR agonist dexmedetomidine. METHODS: DHV constriction responses to a local infusion of dexmedetomidine were assessed by measuring changes in vein diameter with a linear variable differential transformer. The outcome variable for constriction was log-transformed dexmedetomidine ED50. A genome-wide association study (GWAS) of 433 378 single-nucleotide polymorphisms (SNPs) was carried out for determining the sensitivity of DHV responses in 64 healthy Finnish individuals. Twenty SNPs were selected on the basis of the GWAS results and their associations with the ED50 of dexmedetomidine were tested in an independent North American study population of 68 healthy individuals. RESULTS: In both study populations (GWAS and replication samples), the SNP rs9922316 in the gene for protein kinase C type β was consistently associated with dexmedetomidine ED50 for DHV constriction (unadjusted P=0.00016 for the combined population). CONCLUSION: Genetic variation in protein kinase C type β may contribute toward the interindividual variation in DHV constriction responses to α2-AR activation by the agonist dexmedetomidine.
Pharmacogenetics and Genomics 01/2013; · 3.48 Impact Factor
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Marian Beekman,
Hélène Blanché, Markus Perola,
Anti Hervonen,
Vladyslav Bezrukov,
Ewa Sikora,
Frederieke Flachsbart,
Lene Christiansen,
Anton J M De Craen,
Thomas B L Kirkwood, [......],
Stefan Schreiber,
Mark Lathrop,
Axel Skytthe,
Rudi G J Westendorp,
Kaare Christensen,
Jutta Gampe,
Almut Nebel,
Jeanine J Houwing-Duistermaat,
P Eline Slagboom,
Claudio Franceschi
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ABSTRACT: Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in fifteen study centers of eleven European countries as part of the Genetics of Healthy Ageing (GEHA) project. In the joint linkage analyses we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD=3.47), chromosome 17q12-q22 (LOD=2.95), chromosome 19p13.3-p13.11 (LOD=3.76) and chromosome 19q13.11-q13.32 (LOD=3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1,228 unrelated nonagenarian and 1,907 geographically matched controls. Using a fixed effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (p-value=9.6 x 10(-8) ). By combined modeling of linkage and association we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with p-value=0.02 and p-value=1.0 x 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22 and 19p13.3-p13.11. Since the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
Aging cell 01/2013; · 7.55 Impact Factor
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Matthijs J H M van der Loos,
Cornelius A Rietveld,
Niina Eklund,
Philipp D Koellinger,
Fernando Rivadeneira,
Gonçalo R Abecasis,
Georgina A Ankra-Badu,
Sebastian E Baumeister,
Daniel J Benjamin,
Reiner Biffar, [......],
Henry Völzke,
H-Erich Wichmann,
Philipp S Wild,
Sara M Willems,
Gonneke Willemsen,
Frank J A van Rooij,
Patrick J F Groenen,
André G Uitterlinden,
Albert Hofman,
A Roy Thurik
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ABSTRACT: Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg (2)/σP (2) = 25%, h (2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5) were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.
PLoS ONE 01/2013; 8(4):e60542. · 4.09 Impact Factor
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Anna Köttgen,
Eva Albrecht,
Alexander Teumer,
Veronique Vitart,
Jan Krumsiek,
Claudia Hundertmark,
Giorgio Pistis,
Daniela Ruggiero,
Conall M O'Seaghdha,
Toomas Haller, [......],
Nicole Soranzo,
Daniela Toniolo,
Daniel I Chasman,
Olli Raitakari,
W H Linda Kao,
Marina Ciullo,
Caroline S Fox,
Mark Caulfield,
Murielle Bochud,
Christian Gieger
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ABSTRACT: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Nature genetics. 01/2013; 45(2):145-54.
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Anna Köttgen,
Eva Albrecht,
Alexander Teumer,
Veronique Vitart,
Jan Krumsiek,
Claudia Hundertmark,
Giorgio Pistis,
Daniela Ruggiero,
Conall M O'Seaghdha,
Toomas Haller, [......],
Nicole Soranzo,
Daniela Toniolo,
Daniel I Chasman,
Olli Raitakari,
W H Linda Kao,
Marina Ciullo,
Caroline S Fox,
Mark Caulfield,
Murielle Bochud,
Christian Gieger
[show abstract]
[hide abstract]
ABSTRACT: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Nature Genetics 12/2012; · 35.53 Impact Factor
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The CARDIoGRAMplusC4D Consortium,
Panos Deloukas,
Stavroula Kanoni,
Christina Willenborg,
Martin Farrall,
Themistocles L Assimes,
John R Thompson,
Erik Ingelsson,
Danish Saleheen,
Jeanette Erdmann, [......],
Anders Hamsten,
Jaspal S Kooner,
Unnur Thorsteinsdottir,
John Danesh,
Colin N A Palmer,
Robert Roberts,
Hugh Watkins,
Heribert Schunkert,
Nilesh J Samani,
Klaus Stark
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[hide abstract]
ABSTRACT: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
Nature Genetics 12/2012; 45(1):25. · 35.53 Impact Factor
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The CARDIoGRAMplusC4D Consortium,
Panos Deloukas,
Stavroula Kanoni,
Christina Willenborg,
Martin Farrall,
Themistocles L Assimes,
John R Thompson,
Erik Ingelsson,
Danish Saleheen,
Jeanette Erdmann, [......],
Sekar Kathiresan,
Anders Hamsten,
Jaspal S Kooner,
Unnur Thorsteinsdottir,
John Danesh,
Colin N A Palmer,
Robert Roberts,
Hugh Watkins,
Heribert Schunkert,
Nilesh J Samani
[show abstract]
[hide abstract]
ABSTRACT: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
Nature Genetics 12/2012; 45(1):25. · 35.53 Impact Factor
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The CARDIoGRAMplusC4D Consortium,
Panos Deloukas,
Stavroula Kanoni,
Christina Willenborg,
Martin Farrall,
Themistocles L Assimes,
John R Thompson,
Erik Ingelsson,
Danish Saleheen,
Jeanette Erdmann, [......],
Sekar Kathiresan,
Anders Hamsten,
Jaspal S Kooner,
Unnur Thorsteinsdottir,
John Danesh,
Colin N A Palmer,
Robert Roberts,
Hugh Watkins,
Heribert Schunkert,
Nilesh J Samani
[show abstract]
[hide abstract]
ABSTRACT: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
Nature Genetics 12/2012; 45(1):25. · 35.53 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Background. Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. Method. APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. Results. Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. Conclusions. Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.
Annals of medicine 10/2012; · 3.52 Impact Factor
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Ida Surakka,
John B Whitfield, Markus Perola,
Peter M Visscher,
Grant W Montgomery,
Mario Falchi,
Gonneke Willemsen,
Eco J C de Geus,
Patrik K E Magnusson,
Kaare Christensen, [......],
Ann-Christine Syvänen,
Aarno Palotie,
Jaakko Kaprio,
Kirsten O Kyvik,
Nancy L Pedersen,
Dorret I Boomsma,
Tim Spector,
Nicholas G Martin,
Samuli Ripatti,
Leena Peltonen
[show abstract]
[hide abstract]
ABSTRACT: Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene-environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10-8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10-8).
Twin Research and Human Genetics 10/2012; · 1.70 Impact Factor
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[show abstract]
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ABSTRACT: BACKGROUND: In a prospective cohort of consecutive acute coronary syndrome (ACS) patients, we compared the adherence rate of statin usage and mortality rate during a median follow-up of 23 months. HYPOTHESIS: Adherence to statin therapy after acute coronary syndrome affects mortality rate. METHODS: We analyzed ACS patients (N = 1969; age, 65.9 ± 11.8 years; female 30.4%) who underwent angiography between March 2006 and March 2008. The postdischarge usage of statins was based on the purchase register of the Social Insurance Institution of Finland. The death rate was verified from Statistics Finland. RESULTS: At discharge, the rate of statin prescription to patients was 95.4% (n = 1878). When comparing adherent patients (n = 1200; 61.7%), who purchased the medication systematically until the end of the median 23-month follow-up, with nonadherent patients (n = 94; 4.8%), who did not use the medication at all, there was a vast difference in absolute death rate between the groups: 4.9% vs 14.9%, respectively (P < 0.001). We conducted Cox proportional hazards model with ACS type, cerebrovascular attack, diabetes, age, 3-artery disease, and cancer as adjusted confounders. Compared with regular statin users, nonusers were associated with a >2× increased hazard ratio of mortality (hazard ratio: 2.70, 95% confidence interval: 1.49-4.90, P = 0.001). CONCLUSIONS: Statin medication is essential for discharged ACS patients. They should be strongly encouraged to purchase and use it. The authors have no funding, financial relationships, or conflicts of interest to disclose.
Clinical Cardiology 09/2012; · 2.15 Impact Factor
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Tanya M Teslovich,
Kiran Musunuru,
Albert V Smith,
Andrew C Edmondson,
Ioannis M Stylianou,
Masahiro Koseki,
James P Pirruccello,
Samuli Ripatti,
Daniel I Chasman,
Cristen J Willer, [......],
Heribert Schunkert,
L Adrienne Cupples,
Manjinder S Sandhu,
Paul M Ridker,
Daniel J Rader,
Cornelia M van Duijn,
Leena Peltonen,
Gonçalo R Abecasis,
Michael Boehnke,
Sekar Kathiresan
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Tanya M Teslovich,
Kiran Musunuru,
Albert V Smith,
Andrew C Edmondson,
Ioannis M Stylianou,
Masahiro Koseki,
James P Pirruccello,
Samuli Ripatti,
Daniel I Chasman,
Cristen J Willer, [......],
Heribert Schunkert,
L Adrienne Cupples,
Manjinder S Sandhu,
Paul M Ridker,
Daniel J Rader,
Cornelia M van Duijn,
Leena Peltonen,
Gonçalo R Abecasis,
Michael Boehnke,
Sekar Kathiresan
