Circulation: Cardiovascular Genetics最新文献

{"title":"<i>CKM</i> Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia.","authors":"Moneeza Kalhan Siddiqui, Abirami Veluchamy, Cyrielle Maroteau, Roger Tavendale, Fiona Carr, Ewan Pearson, Helen Colhoun, Andrew D Morris, Jacob George, Alexander Doney, Munir Pirmohamed, Ana Alfirevic, Mia Wadelius, Anke H Maitland van der Zee, Paul M Ridker, Daniel I Chasman, Colin N A Palmer","doi":"10.1161/CIRCGENETICS.117.001737","DOIUrl":"10.1161/CIRCGENETICS.117.001737","url":null,"abstract":"<p><strong>Background: </strong>To test the association of a recently reported variant in the creatine kinase (CK) muscle gene, <i>CKM</i> Glu83Gly (rs11559024) with constitutive creatine phosphokinase (CK) levels, CK variation, and inducibility. Given the diagnostic importance of CK in determining muscle damage, we tested the association of the variant with myalgia.</p><p><strong>Methods and results: </strong>Meta-analysis between longitudinal cohort GoDARTS (Genetics of Diabetes Audit and Research, Tayside Scotland), minor allele frequency (=0.02), and randomized clinical trial (JUPITER [Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin], minor allele frequency=0.018) was used to replicate the association with baseline CK measures. GoDARTS was used to study the relationship with CK variability. Myalgia was studied in JUPITER trial participants. Baseline and SDs of CK were on average 18% (<i>P</i> value=6×10^-⁶³) and 24% (<i>P</i> value=2×10^-5) lower for carriers of the variant, respectively. The variant was not associated with myalgia (odds ratio, 0.84; 95% confidence interval, 0.52-1.38).</p><p><strong>Conclusions: </strong>This study highlights that a genetic factor known to be associated with constitutive CK levels is also associated with CK variability and inducibility. This is discussed in the context of evidence to suggest that the variant has an impact on inducibility of CK by trauma through a previously reported case of a homozygous carrier. However, the lack of association between the variant and myalgia suggests that it cannot reliably be used as a biomarker for muscle symptoms.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35393653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Disease and Long Noncoding RNAs: Tools for Unraveling the Mystery Lnc-ing RNA and Phenotype.","authors":"Elizabeth J Hennessy","doi":"10.1161/CIRCGENETICS.117.001556","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001556","url":null,"abstract":"The last decade has ushered in a surge of genetic information with budget-friendly and more efficient sequencing technologies adding to our understanding of human development and disease. The sequencing of the human genome was a remarkable feat, yet using this information to understand human health and disease has proven to be challenging. The mammalian genome is comprised of a complex infrastructure of defined nucleotide sequences and dynamic epigenetic modifications that result in shifts in gene expression patterns and subsequent developmental and phenotypic outcomes. Genome wide association studies (GWAS) have demonstrated the link between alterations in nucleotide sequences created by mutations, such as single nucleotide polymorphisms (SNPs) and disease. However, it remains unclear how SNPs alter gene expression patterns and phenotypes. One hypothesis links SNP containing regions to mutational phenotypes via changes to epigenetic processes that control how genes are regulated, such as DNA methylation and histone acetylation.\u0000\u0000SNPs are changes in nucleotide sequences that occur in at least 1% of the population. It is estimated that there are 10 to 30 million SNPs in humans that occur every 100 to 300 bases, and this variation is the major source of heterogeneity among people. A nonsynonymous SNP changes the amino acid sequence of a protein-coding gene. Less than 10% of SNPs are nonsynonymous, whereas 90% occur in nonprotein coding regions of the genome.1 SNPs can be found in regions of deoxyribonuclease I (DNase I) hypersensitivity or promoters affecting transcription factor–binding sites and chromatin state. SNPs can create or delete microRNA-binding sites in 3′ untranslated regions (UTRs) affecting microRNA target mRNA expression.2 SNPs can also be found in regions expressing noncoding RNAs, such as long noncoding RNAs (lncRNAs) leading to alterations in their expression patterns. SNPs can affect alternative splicing and the secondary structure of an RNA transcript leading to …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001556"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1161/HCG.0000000000000038","DOIUrl":"https://doi.org/10.1161/HCG.0000000000000038","url":null,"abstract":"","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e000038"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/HCG.0000000000000038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35313239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.","authors":"Ingrid E Christophersen,&nbsp;Jared W Magnani,&nbsp;Xiaoyan Yin,&nbsp;John Barnard,&nbsp;Lu-Chen Weng,&nbsp;Dan E Arking,&nbsp;Maartje N Niemeijer,&nbsp;Steven A Lubitz,&nbsp;Christy L Avery,&nbsp;Qing Duan,&nbsp;Stephan B Felix,&nbsp;Joshua C Bis,&nbsp;Kathleen F Kerr,&nbsp;Aaron Isaacs,&nbsp;Martina Müller-Nurasyid,&nbsp;Christian Müller,&nbsp;Kari E North,&nbsp;Alex P Reiner,&nbsp;Lesley F Tinker,&nbsp;Jan A Kors,&nbsp;Alexander Teumer,&nbsp;Astrid Petersmann,&nbsp;Moritz F Sinner,&nbsp;Petra Buzkova,&nbsp;Jonathan D Smith,&nbsp;David R Van Wagoner,&nbsp;Uwe Völker,&nbsp;Melanie Waldenberger,&nbsp;Annette Peters,&nbsp;Thomas Meitinger,&nbsp;Marian C Limacher,&nbsp;Kirk C Wilhelmsen,&nbsp;Bruce M Psaty,&nbsp;Albert Hofman,&nbsp;Andre Uitterlinden,&nbsp;Bouwe P Krijthe,&nbsp;Zhu-Ming Zhang,&nbsp;Renate B Schnabel,&nbsp;Stefan Kääb,&nbsp;Cornelia van Duijn,&nbsp;Jerome I Rotter,&nbsp;Nona Sotoodehnia,&nbsp;Marcus Dörr,&nbsp;Yun Li,&nbsp;Mina K Chung,&nbsp;Elsayed Z Soliman,&nbsp;Alvaro Alonso,&nbsp;Eric A Whitsel,&nbsp;Bruno H Stricker,&nbsp;Emelia J Benjamin,&nbsp;Susan R Heckbert,&nbsp;Patrick T Ellinor","doi":"10.1161/CIRCGENETICS.116.001667","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001667","url":null,"abstract":"<p><strong>Background: </strong>The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.</p><p><strong>Methods and results: </strong>We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (<i>P</i><5×10^-⁸) novel loci and replicated a prior association with S<i>CN10A.</i> We identified 3 loci at <i>SCN5A</i>, <i>TBX5</i>, and <i>CAV1/CAV2</i> that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.</p><p><strong>Conclusions: </strong>We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35399915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Disclosing Genetic Risk for Coronary Heart Disease on Information Seeking and Sharing: The MI-GENES Study (Myocardial Infarction Genes).","authors":"Sherry-Ann N Brown,&nbsp;Hayan Jouni,&nbsp;Tariq S Marroush,&nbsp;Iftikhar J Kullo","doi":"10.1161/CIRCGENETICS.116.001613","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001613","url":null,"abstract":"<p><strong>Background: </strong>Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. We hypothesized that disclosing genetic risk for CHD to individuals influences information seeking and sharing.</p><p><strong>Methods and results: </strong>The MI-GENES study (Myocardial Infarction Genes) randomized participants (n=203) aged 45 to 65 years who were at intermediate CHD risk based on conventional risk factors and not on statins to receive their conventional risk score alone or also a genetic risk score based on 28 variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys assessing information seeking were completed before and after risk disclosure. Information sharing was assessed post-disclosure. Six-month post-disclosure, genetic risk score participants were more likely than conventional risk score participants to visit a website to learn about CHD (odds ratio [OR], 4.88 [confidence interval (CI), 1.55-19.13]; <i>P</i>=0.01), use the internet for information about how genetic factors affect CHD risk (OR, 2.11 [CI, 1.03-4.47]; <i>P</i>=0.04), access their CHD risk via a patient portal (OR, 2.99 [CI, 1.35-7.04]; <i>P</i>=0.01), and discuss their CHD risk with others (OR, 3.13 [CI, 1.41-7.47]; <i>P</i>=0.01), particularly their siblings (OR, 1.92 [CI, 1.06-3.51]; <i>P</i>=0.03), extended family (OR, 3.8 [CI, 1.37-12.38]; <i>P=</i>0.01), coworkers (OR, 2.42 [CI, 1.09-5.76]; <i>P</i>=0.03), and primary care provider (PCP; OR, 2.00 [CI, 1.08-3.75]; <i>P</i>=0.03).</p><p><strong>Conclusions: </strong>Disclosure of a genetic risk score for CHD increased information seeking and sharing.</p><p><strong>Clinical trial registration: </strong>URL: https://clinicaltrials.gov/. Unique identifier: NCT01936675.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35384203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy.","authors":"Saskia Haitjema, Daniel Kofink, Jessica van Setten, Sander W van der Laan, Arjan H Schoneveld, James Eales, Maciej Tomaszewski, Saskia C A de Jager, Gerard Pasterkamp, Folkert W Asselbergs, Hester M den Ruijter","doi":"10.1161/CIRCGENETICS.116.001544","DOIUrl":"10.1161/CIRCGENETICS.116.001544","url":null,"abstract":"<p><strong>Background: </strong>Recent studies found an immune regulatory role for Y chromosome and a relationship between loss of Y chromosome (LOY) in blood cells and a higher risk of cancer and mortality. Given involvement of immune cells in atherosclerosis, we hypothesized that LOY is associated with the severity of atherosclerotic plaque characteristics and outcome in men undergoing carotid endarterectomy.</p><p><strong>Methods and results: </strong>LOY was quantified in blood and plaque from raw intensity genotyping data in men within the Athero-Express biobank study. Plaques were dissected, and the culprit lesions used for histology and the measurement of inflammatory proteins. We tested LOY for association with (inflammatory) atherosclerotic plaque phenotypes and cytokines and assessed the association of LOY with secondary events during 3-year follow-up. Of 366 patients with carotid endarterectomy, 61 exhibited some degree of LOY in blood. LOY was also present in atherosclerotic plaque lesions (n=8/242, 3%). LOY in blood was negatively associated with age (β=-0.03/10 y; <i>r</i>²=0.07; <i>P</i>=1.6×10^-7) but not with cardiovascular disease severity at baseline. LOY in blood was associated with a larger atheroma size (odds ratio, 2.15; 95% confidence interval, 1.06-4.76; <i>P</i>=0.04); however, this association was not significant after correction for multiple testing. LOY was independently associated with secondary major cardiovascular events (hazard ratio=2.28; 95% confidence interval, 1.11-4.67; <i>P</i>=0.02) in blood when corrected for confounders.</p><p><strong>Conclusions: </strong>In this hypothesis-generating study, LOY in blood is independently associated with secondary major cardiovascular events in a severely atherosclerotic population. Our data could indicate that LOY affects secondary outcome via other mechanisms than inflammation in the atherosclerotic plaque.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001544"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PCSK9</i> Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.","authors":"Shia T Kent, Robert S Rosenson, Christy L Avery, Yii-Der I Chen, Adolfo Correa, Steven R Cummings, L Adrienne Cupples, Mary Cushman, Daniel S Evans, Vilmundur Gudnason, Tamara B Harris, George Howard, Marguerite R Irvin, Suzanne E Judd, J Wouter Jukema, Leslie Lange, Emily B Levitan, Xiaohui Li, Yongmei Liu, Wendy S Post, Iris Postmus, Bruce M Psaty, Jerome I Rotter, Monika M Safford, Colleen M Sitlani, Albert V Smith, James D Stewart, Stella Trompet, Fangui Sun, Ramachandran S Vasan, J Michael Woolley, Eric A Whitsel, Kerri L Wiggins, James G Wilson, Paul Muntner","doi":"10.1161/CIRCGENETICS.116.001632","DOIUrl":"10.1161/CIRCGENETICS.116.001632","url":null,"abstract":"<p><strong>Background: </strong><i>PCSK9</i> loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of <i>PCSK9</i> LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy.</p><p><strong>Methods and results: </strong>These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between <i>PCSK9</i> LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, <i>PCSK9</i> LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. <i>PCSK9</i> LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. <i>PCSK9</i> LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites).</p><p><strong>Conclusions: </strong><i>PCSK9</i> LOF variants were associated with lower LDL-C and coronary heart disease incidence. <i>PCSK9</i> LOF variants were not associated with stroke risk.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001632"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729040/pdf/nihms889818.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association.","authors":"Kiran Musunuru,&nbsp;Erik Ingelsson,&nbsp;Myriam Fornage,&nbsp;Peter Liu,&nbsp;Anne M Murphy,&nbsp;L Kristin Newby,&nbsp;Christopher Newton-Cheh,&nbsp;Marco V Perez,&nbsp;Deepak Voora,&nbsp;Daniel Woo","doi":"10.1161/HCG.0000000000000037","DOIUrl":"https://doi.org/10.1161/HCG.0000000000000037","url":null,"abstract":"<p><p>There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the \"expressed genome.\" The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/HCG.0000000000000037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35277962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Informational Quest.","authors":"Susanne B Haga","doi":"10.1161/CIRCGENETICS.117.001860","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001860","url":null,"abstract":"","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35384206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events.","authors":"Jan P Dumanski,&nbsp;Johan Sundström,&nbsp;Lars A Forsberg","doi":"10.1161/CIRCGENETICS.117.001820","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001820","url":null,"abstract":"It has been observed for centuries that men have a shorter lifespan than women. The current difference globally is on average 4 years, and the difference is even larger in populations with longer life expectancy, for example, ≈6 years in the European Union and 7 years in Japan.1 A larger difference in populations with higher longevity suggests that the underlying factors are stronger in populations with a large part of the mortality related to age-associated diseases. Cardiovascular diseases are the leading causes of death globally and are increasing.2 The share of total mortality that is because of cardiovascular diseases is similar in both sexes, but men fall ill and die from it at a younger age. Cardiovascular disease risk factors are equally important for men and women.3 Hence, the age differences in incidence and mortality between men and women are because of other reasons than differential environmental risk factor exposures. Recent discoveries on pathological effects from a male-specific genetic risk factor—loss of chromosome Y (LOY) in blood cells—can partly explain the observed sex difference in longevity. Analyses by Haitjema et al4 in this issue of Circulation: Cardiovascular Genetics describe a previously unknown association between LOY in blood cells and major cardiovascular events.\u0000\u0000See Article by Haitjema et al \u0000\u0000A high prevalence …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001820"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}