Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

The genomics of heart failure: design and rationale of the HERMES consortium

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.</p

The genomics of heart failure: design and rationale of the HERMES consortium

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P &lt; 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Arbetsinriktad rehabilitering för personer med utmattningssyndrom : Vad i rehabiliteringen har klienterna upplevt vara mest verksamt?

Stress related long term illness for depression, anxiety, and chronic fatigue syndrome has increased dramatically in the last decade in Sweden and discussions about what should be included in a rehabilitation program for individuals with chronic fatigue syndrome continues. How rehabilitation is implemented is crucial for recovery and return to work. What in the work rehabilitation of people with chronic fatigue syndrome is perceived as most effective is, thus, important to take note of. Have the rehabilitation contributed to perceived improvements? What in the rehabilitation has been most appreciated and what can be done better? This thesis was based on the clients´ perspectives and experiences, not tied to a particular method. With the model a "Sense of Coherence" (SOC) (Antonovsky, 2009), as a foundation, a questionnaire regarding areas within rehabilitation and perceived quality of life, before and after the rehabilitation, was formed. Eight people diagnosed with chronic fatigue syndrome were interviewed. The results were analyzed with a thematic analysis method. The patterns and themes were related to the SOC model to see if the results could be understood and interpreted with the model. The results show that the rehabilitation had a positive effect on health and quality of life and that the totality of the measures had the greatest impact, with great improvements as a result.Validerat; 20140620 (global_studentproject_submitter

Schwierigkeiten bei der Buchhaltung laut IAS/IFRS

Börsnoterade europeiska företag ska från och med 1 januari 2005 tillämpa de internationella redovisningsstandarder som antagits av EU. Standarderna benämns International Accounting Reporting Standard, IAS och International Financial Reporting Standard, IFRS. Dessa standarder ska tillämpas vid företagens koncernredovisning, medan nationell lagstiftning gäller för resterande finansiella rapporter. Syftet med denna uppsats är att ta reda på vilka svårigheter som kan finnas med att redovisa enligt IAS/IFRS. Till vår hjälp för att få fram information om detta har vi använt oss av det svenska dotterbolaget till den multinationella läkemedelskoncernen AstraZeneca, Rådet för finansiell rapportering samt en revisor på Ernst &amp; Young. Vi valde att använda oss av en kvalitativ metod och gjorde fyra intervjuer för att få så ingående information som möjligt. Vid intervjuerna användes öppna frågor för att få en tydlig beskrivning av svårigheterna. Teoriavsnittet inleds med ett avsnitt om svårigheter som kan uppkomma vid implementeringen och användningen av IAS/IFRS. Därefter beskrivs redovisningen i Sverige. Sedan följer en bakgrund till de internationella redovisningsstandarderna, vilka kriterier som gäller när dessa ska upprättas, samt information om den svenska normgivningen. Avslutningsvis beskrivs i teoriavsnittet de standarder där de flesta svårigheterna har framkommit. Empirin består av de intervjuer som genomförts. Varje intervju inleds med en kort presentation av respondenten och dennes arbetsplats. Informationen som framkommer i empirin leder sedan till analysen. Där sammanförs empirin med tidigare beskriven teori. Vi kom fram till att det finns flera svårigheter med att redovisa enligt IAS/IFRS. Många svårigheter rör värdering i olika former samt att svensk normgivning inte alltid följer det internationella regelverket, vilket orsakar dubbel redovisning. Det framkom även att IAS/IFRS upplevs som ett komplext regelverk med i många fall alltför detaljrika informationskrav

Svårigheter med att redovisa enligt IAS/IFRS

Börsnoterade europeiska företag ska från och med 1 januari 2005 tillämpa de internationella redovisningsstandarder som antagits av EU. Standarderna benämns International Accounting Reporting Standard, IAS och International Financial Reporting Standard, IFRS. Dessa stan¬darder ska tillämpas vid företagens koncernredovisning, medan nationell lagstiftning gäller för resterande finansiella rapporter. Syftet med denna uppsats är att ta reda på vilka svårigheter som kan finnas med att redovisa enligt IAS/IFRS. Till vår hjälp för att få fram information om detta har vi använt oss av det svenska dotterbolaget till den multinationella läkemedelskoncernen AstraZeneca, Rådet för finansiell rapportering samt en revisor på Ernst &amp; Young. Vi valde att använda oss av en kvalitativ metod och gjorde fyra intervjuer för att få så ingå¬ende information som möjligt. Vid intervjuerna användes öppna frågor för att få en tydlig be¬skrivning av svårigheterna. Teoriavsnittet inleds med ett avsnitt om svårigheter som kan uppkomma vid implemente¬ringen och användningen av IAS/IFRS. Därefter beskrivs redovisningen i Sverige. Sedan följer en bakgrund till de internationella redovisningsstandarderna, vilka kriterier som gäller när dessa ska upprättas, samt information om den svenska normgivningen. Avslutningsvis be¬skrivs i teoriavsnittet de standarder där de flesta svårigheterna har framkommit. Empirin består av de intervjuer som genomförts. Varje intervju inleds med en kort presenta¬tion av respondenten och dennes arbetsplats. Informationen som framkommer i empirin leder sedan till analysen. Där sammanförs empirin med tidigare beskriven teori. Vi kom fram till att det finns flera svårigheter med att redovisa enligt IAS/IFRS. Många svå¬righeter rör värdering i olika former samt att svensk normgivning inte alltid följer det interna¬tionella regelverket, vilket orsakar dubbel redovisning. Det framkom även att IAS/IFRS upp¬levs som ett komplext regelverk med i många fall alltför detaljrika informationskrav