An epigenome-wide association study of sex-specific chronological ageing.

Abstract:

BACKGROUND:Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in blood-based DNA methylation in an unrelated cohort of 2586 individuals between the ages of 18 and 87 years, with replication in a further 4450 individuals between the ages of 18 and 93 years. METHODS:Linear regression models were applied, with stringent genome-wide significance thresholds (p < 3.6 × 10-8) used in both the discovery and replication data. A second, highly conservative mixed linear model method that better controls the false-positive rate was also applied, using the same genome-wide significance thresholds. RESULTS:Using the linear regression method, 52 autosomal and 597 X-linked CpG sites, mapping to 251 unique genes, replicated with concordant effect size directions in the age-by-sex interaction analysis. The site with the greatest difference mapped to GAGE10, an X-linked gene. Here, DNA methylation levels remained stable across the male adult age range (DNA methylation by age r = 0.02) but decreased across female adult age range (DNA methylation by age r = - 0.61). One site (cg23722529) with a significant age-by-sex interaction also had a quantitative trait locus (rs17321482) that is a genome-wide significant variant for prostate cancer. The mixed linear model method identified 11 CpG sites associated with the age-by-sex interaction. CONCLUSION:The majority of differences in age-associated DNA methylation trajectories between sexes are present on the X chromosome. Several of these differences occur within genes that have been implicated in sexually dimorphic traits.

journal_name

Genome Med

journal_title

Genome medicine

authors

McCartney DL,Zhang F,Hillary RF,Zhang Q,Stevenson AJ,Walker RM,Bermingham ML,Boutin T,Morris SW,Campbell A,Murray AD,Whalley HC,Porteous DJ,Hayward C,Evans KL,Chandra T,Deary IJ,McIntosh AM,Yang J,Visscher PM,McRa

doi

10.1186/s13073-019-0693-z

subject

Has Abstract

pub_date

2019-12-31 00:00:00

pages

1

issue

1

issn

1756-994X

pii

10.1186/s13073-019-0693-z

journal_volume

12

pub_type

杂志文章
  • Huntington's disease: the case for genetic modifiers.

    abstract::For almost three decades, Huntington's disease has been a prototype for the application of genetic strategies to human disease. HD, the Huntington's disease gene, was the first autosomal defect mapped using only DNA markers, a finding in 1983 that helped to spur similar studies in many other disorders and contributed ...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm80

    authors: Gusella JF,MacDonald ME

    更新日期:2009-08-21 00:00:00

  • Immunoinformatics and epitope prediction in the age of genomic medicine.

    abstract::Immunoinformatics involves the application of computational methods to immunological problems. Prediction of B- and T-cell epitopes has long been the focus of immunoinformatics, given the potential translational implications, and many tools have been developed. With the advent of next-generation sequencing (NGS) metho...

    journal_title:Genome medicine

    pub_type: 杂志文章,评审

    doi:10.1186/s13073-015-0245-0

    authors: Backert L,Kohlbacher O

    更新日期:2015-11-20 00:00:00

  • An ethics safe harbor for international genomics research?

    abstract:BACKGROUND:Genomics research is becoming increasingly globally connected and collaborative, contesting traditional ethical and legal boundaries between global and local research practice. As well, global data-driven genomics research holds great promise for health discoveries. Yet, paradoxically, current research ethic...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm503

    authors: Dove ES,Knoppers BM,Zawati MH

    更新日期:2013-11-22 00:00:00

  • Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation.

    abstract:BACKGROUND:Wnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized. METHODS:We comprehensively m...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00788-5

    authors: Liu S,Harmston N,Glaser TL,Wong Y,Zhong Z,Madan B,Virshup DM,Petretto E

    更新日期:2020-10-22 00:00:00

  • Cancer detection and biopsy classification using concurrent histopathological and metabolomic analysis of core biopsies.

    abstract:BACKGROUND:Metabolomics, the non-targeted interrogation of small molecules in a biological sample, is an ideal technology for identifying diagnostic biomarkers. Current tissue extraction protocols involve sample destruction, precluding additional uses of the tissue. This is particularly problematic for high value sampl...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm332

    authors: Brown MV,McDunn JE,Gunst PR,Smith EM,Milburn MV,Troyer DA,Lawton KA

    更新日期:2012-04-30 00:00:00

  • Back to the family: a renewed approach to rare variant studies.

    abstract::A report on the 62nd Annual Meeting of the American Society of Human Genetics, San Francisco, California, USA, 6-10 November 2012. ...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm398

    authors: Zielinski D,Gymrek M,Erlich Y

    更新日期:2012-12-19 00:00:00

  • High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine.

    abstract:BACKGROUND:Neisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-017-0400-x

    authors: O'Connor D,Clutterbuck EA,Thompson AJ,Snape MD,Ramasamy MN,Kelly DF,Pollard AJ

    更新日期:2017-01-30 00:00:00

  • Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease.

    abstract:BACKGROUND:Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results are stored in electronic health records (EHRs), and a growing number of EHRs are linked to patient DNA, offering unprecedented opportunities to query relationships between genetic ri...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00820-8

    authors: Dennis JK,Sealock JM,Straub P,Lee YH,Hucks D,Actkins K,Faucon A,Feng YA,Ge T,Goleva SB,Niarchou M,Singh K,Morley T,Smoller JW,Ruderfer DM,Mosley JD,Chen G,Davis LK

    更新日期:2021-01-13 00:00:00

  • A comparison of epigenetic mitotic-like clocks for cancer risk prediction.

    abstract:BACKGROUND:DNA methylation changes that accrue in the stem cell pool of an adult tissue in line with the cumulative number of cell divisions may contribute to the observed variation in cancer risk among tissues and individuals. Thus, the construction of epigenetic "mitotic" clocks that can measure the lifetime number o...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00752-3

    authors: Teschendorff AE

    更新日期:2020-06-24 00:00:00

  • De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.

    abstract:BACKGROUND:Molecular diagnostics can resolve locus heterogeneity underlying clinical phenotypes that may otherwise be co-assigned as a specific syndrome based on shared clinical features, and can associate phenotypically diverse diseases to a single locus through allelic affinity. Here we describe an apparently novel s...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm415

    authors: Bainbridge MN,Hu H,Muzny DM,Musante L,Lupski JR,Graham BH,Chen W,Gripp KW,Jenny K,Wienker TF,Yang Y,Sutton VR,Gibbs RA,Ropers HH

    更新日期:2013-02-05 00:00:00

  • Environment-driven somatic mosaicism in brain disorders.

    abstract::The identification of somatic mosaicism in the brain lends a new perspective to our understanding of the role of gene and environment interactions in psychiatric disease risk. Somatic mutations, such as retrotransposon insertions, that are precipitated by modern environmental factors may alter neuronal function and ne...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-016-0317-9

    authors: Bedrosian TA,Linker S,Gage FH

    更新日期:2016-05-23 00:00:00

  • Multi-locus models of genetic risk of disease.

    abstract:BACKGROUND:Evidence for genetic contribution to complex diseases is described by recurrence risks to relatives of diseased individuals. Genome-wide association studies allow a description of the genetics of the same diseases in terms of risk loci, their effects and allele frequencies. To reconcile the two descriptions ...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm131

    authors: Wray NR,Goddard ME

    更新日期:2010-02-02 00:00:00

  • Using inactivating mutations to provide insight into drug action.

    abstract::The role of ezetimibe in lowering plasma cholesterol has been established; however, controversy remains about its clinical benefit. A recent study utilizes naturally occurring genetic variation within the NPC1-like 1 gene (NPC1L1) to demonstrate the potential for pharmacologic inhibition of the protein to reduce the r...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0130-x

    authors: Corbin LJ,Timpson NJ

    更新日期:2015-01-28 00:00:00

  • Progress in the use of RNA interference as a therapy for chronic hepatitis B virus infection.

    abstract::Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for hepatocellular carcinoma and cirrhosis. Current treatment regimens, which include interferon-alpha and nucleoside/nucleotide analogs, are only partially effective and new treatm...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm149

    authors: Weinberg MS,Arbuthnot P

    更新日期:2010-04-28 00:00:00

  • The three-body problem of therapy with induced pluripotent stem cells.

    abstract::Regenerative medicine has a three-body problem: alignment of the dynamics of the genome, stem cell and patient. Focusing on the rare inherited fragile skin disorder epidermolysis bullosa, three recent innovative studies have used induced pluripotent stem cells and gene correction, revertant mosaicism or genome editing...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0141-7

    authors: Tolar J,McGrath JA

    更新日期:2015-02-20 00:00:00

  • A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens.

    abstract::Whole genome sequencing is increasingly used to study phenotypic variation among infectious pathogens and to evaluate their relative transmissibility, virulence, and immunogenicity. To date, relatively little has been published on how and how many pathogen strains should be selected for studies associating phenotype a...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-014-0101-7

    authors: Farhat MR,Shapiro BJ,Sheppard SK,Colijn C,Murray M

    更新日期:2014-11-15 00:00:00

  • Creating a data resource: what will it take to build a medical information commons?

    abstract::National and international public-private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-017-0476-3

    authors: Deverka PA,Majumder MA,Villanueva AG,Anderson M,Bakker AC,Bardill J,Boerwinkle E,Bubela T,Evans BJ,Garrison NA,Gibbs RA,Gentleman R,Glazer D,Goldstein MM,Greely H,Harris C,Knoppers BM,Koenig BA,Kohane IS,La Rosa S,

    更新日期:2017-09-22 00:00:00

  • Use of semantic workflows to enhance transparency and reproducibility in clinical omics.

    abstract:BACKGROUND:Recent highly publicized cases of premature patient assignment into clinical trials, resulting from non-reproducible omics analyses, have prompted many to call for a more thorough examination of translational omics and highlighted the critical need for transparency and reproducibility to ensure patient safet...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0202-y

    authors: Zheng CL,Ratnakar V,Gil Y,McWeeney SK

    更新日期:2015-07-25 00:00:00

  • Ultradeep analysis of tumor heterogeneity in regions of somatic hypermutation.

    abstract::Tumor heterogeneity is of growing importance in the treatment of cancers. Mutational hot spots are prime locations for determining number and proportions of low variant allele frequency (VAF) tumor subclones by next generation sequencing. Low VAF detection is complicated by poor mapping efficiency in regions with high...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0147-1

    authors: Spence JM,Spence JP,Abumoussa A,Burack WR

    更新日期:2015-03-12 00:00:00

  • Estimating exome genotyping accuracy by comparing to data from large scale sequencing projects.

    abstract::With exome sequencing becoming a tool for mutation detection in routine diagnostics there is an increasing need for platform-independent methods of quality control. We present a genotype-weighted metric that allows comparison of all the variant calls of an exome to a high-quality reference dataset of an ethnically mat...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm473

    authors: Heinrich V,Kamphans T,Stange J,Parkhomchuk D,Hecht J,Dickhaus T,Robinson PN,Krawitz PM

    更新日期:2013-07-31 00:00:00

  • The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls.

    abstract:BACKGROUND:The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have been confirmed to encode different PTPN22 (LYP) proteins, but detailed information regarding...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm301

    authors: Ronninger M,Guo Y,Shchetynsky K,Hill A,Khademi M,Olsson T,Reddy PS,Seddighzadeh M,Clark JD,Lin LL,O'Toole M,Padyukov L

    更新日期:2012-01-20 00:00:00

  • Genome-wide approaches for identifying genetic risk factors for osteoporosis.

    abstract::Osteoporosis, the most common type of bone disease worldwide, is clinically characterized by low bone mineral density (BMD) and increased susceptibility to fracture. Multiple genetic and environmental factors and gene-environment interactions have been implicated in its pathogenesis. Osteoporosis has strong genetic de...

    journal_title:Genome medicine

    pub_type: 杂志文章,评审

    doi:10.1186/gm448

    authors: Wu S,Liu Y,Zhang L,Han Y,Lin Y,Deng HW

    更新日期:2013-05-29 00:00:00

  • A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition.

    abstract:BACKGROUND:Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several differe...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00814-6

    authors: Heiden SE,Hübner NO,Bohnert JA,Heidecke CD,Kramer A,Balau V,Gierer W,Schaefer S,Eckmanns T,Gatermann S,Eger E,Guenther S,Becker K,Schaufler K

    更新日期:2020-12-09 00:00:00

  • Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma.

    abstract:BACKGROUND:Long non-coding RNAs (lncRNAs) are emerging as molecules that significantly impact many cellular processes and have been associated with almost every human cancer. Compared to protein-coding genes, lncRNA genes are often associated with transposable elements, particularly with endogenous retroviral elements ...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0142-6

    authors: Gibb EA,Warren RL,Wilson GW,Brown SD,Robertson GA,Morin GB,Holt RA

    更新日期:2015-03-05 00:00:00

  • VISPA: a computational pipeline for the identification and analysis of genomic vector integration sites.

    abstract::The analysis of the genomic distribution of viral vector genomic integration sites is a key step in hematopoietic stem cell-based gene therapy applications, allowing to assess both the safety and the efficacy of the treatment and to study the basic aspects of hematopoiesis and stem cell biology. Identifying vector int...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-014-0067-5

    authors: Calabria A,Leo S,Benedicenti F,Cesana D,Spinozzi G,Orsini M,Merella S,Stupka E,Zanetti G,Montini E

    更新日期:2014-09-03 00:00:00

  • An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.

    abstract::During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online "immuno-analytics" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid prote...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00822-6

    authors: Ward D,Higgins M,Phelan JE,Hibberd ML,Campino S,Clark TG

    更新日期:2021-01-07 00:00:00

  • Pan-cancer identification of clinically relevant genomic subtypes using outcome-weighted integrative clustering.

    abstract:BACKGROUND:Comprehensive molecular profiling has revealed somatic variations in cancer at genomic, epigenomic, transcriptomic, and proteomic levels. The accumulating data has shown clearly that molecular phenotypes of cancer are complex and influenced by a multitude of factors. Conventional unsupervised clustering appl...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-020-00804-8

    authors: Arora A,Olshen AB,Seshan VE,Shen R

    更新日期:2020-12-03 00:00:00

  • Defining functional signatures of dysbiosis in periodontitis progression.

    abstract::Periodontitis is a common inflammatory disease that leads to tooth loss and has been linked to cardiovascular disease and diabetes mellitus. The periodontal microbiome is highly diverse, and metatranscriptomic studies have indicated that the genes that are expressed by the microbiota are more relevant than the microbi...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/s13073-015-0165-z

    authors: Wang GP

    更新日期:2015-04-27 00:00:00

  • Survey of European clinical geneticists on awareness, experiences and attitudes towards direct-to-consumer genetic testing.

    abstract:BACKGROUND:The advent of direct-to-consumer (DTC) genetic testing (GT) has sparked a number of debates regarding the scientific validity of tests, their broad health and ethical implications for society as well as their legal status. To date, relatively few empirical studies have been published regarding this phenomeno...

    journal_title:Genome medicine

    pub_type: 杂志文章

    doi:10.1186/gm449

    authors: Howard HC,Borry P

    更新日期:2013-05-22 00:00:00

  • Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice.

    abstract::Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significant morbidity and mortality. Although currently classified into distinct disorder categories, they show clinical overlap and f...

    journal_title:Genome medicine

    pub_type: 杂志文章,评审

    doi:10.1186/gm546

    authors: Doherty JL,Owen MJ

    更新日期:2014-04-28 00:00:00