Abstract:
:The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 x THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs-acting either in combination or as single variants--predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Auro K,Alanne M,Kristiansson K,Silander K,Kuulasmaa K,Salomaa V,Peltonen L,Perola Mdoi
10.1371/journal.pgen.0030120subject
Has Abstractpub_date
2007-07-01 00:00:00pages
e120issue
7eissn
1553-7390issn
1553-7404pii
07-PLGE-RA-0034journal_volume
3pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Histone modifiers are critical regulators of chromatin-based processes in eukaryotes. The histone methyltransferase Set1, a component of the Set1C/COMPASS complex, catalyzes the methylation at lysine 4 of histone H3 (H3K4me), a hallmark of euchromatin. Here, we show that the fission yeast Schizosaccharomyces pombe Set...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004740
更新日期:2014-10-30 00:00:00
abstract::Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent of classical risk factors. One such association signal has been identified at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated polymorphism in this region, rs12190287, ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004263
更新日期:2014-03-27 00:00:00
abstract::To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 w...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1002718
更新日期:2012-07-01 00:00:00
abstract::Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and ide...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030145
更新日期:2007-08-01 00:00:00
abstract::Aversive learning and memories are crucial for animals to avoid previously encountered stressful stimuli and thereby increase their chance of survival. Neuropeptides are essential signaling molecules in the brain and are emerging as important modulators of learned behaviors, but their precise role is not well understo...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007945
更新日期:2019-02-19 00:00:00
abstract::Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001354
更新日期:2011-03-01 00:00:00
abstract::Homolog pairing and crossing over during meiosis I prophase is required for accurate chromosome segregation to form euploid gametes. The repair of Spo11-induced double-strand breaks (DSB) using a homologous chromosome template is a major driver of pairing in many species, including fungi, plants, and mammals. Inapprop...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003197
更新日期:2013-01-01 00:00:00
abstract::Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted out...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006096
更新日期:2016-06-06 00:00:00
abstract::In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). Expression of genomic TEs is proposed to initiate self regulation by increasing the production of repressive piRNAs, thereby "adap...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008861
更新日期:2020-06-11 00:00:00
abstract::Most of the somatic cells of adult metazoans, including mammals, do not undergo continuous cycles of replication. Instead, they are quiescent and devote most of their metabolic activity to gene expression. The mutagenic consequences of exposure to DNA-damaging agents are well documented, but less is known about the im...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000577
更新日期:2009-07-01 00:00:00
abstract::A complex program of translational repression, mRNA localization, and translational activation ensures that Oskar (Osk) protein accumulates only at the posterior pole of the Drosophila oocyte. Inappropriate expression of Osk disrupts embryonic axial patterning, and is lethal. A key factor in translational repression i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004992
更新日期:2015-02-27 00:00:00
abstract::Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type-specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogenous glutamine for survival to justify the therapeutic targeting ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002229
更新日期:2011-08-01 00:00:00
abstract::In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside) operon of E. coli. This locus ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000405
更新日期:2009-03-01 00:00:00
abstract::Detailed information about stage-specific changes in gene expression is crucial for the understanding of the gene regulatory networks underlying development. Here, we describe the global gene expression dynamics during early flower development, a key process in the life cycle of a plant, during which floral patterning...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020117.eor
更新日期:2006-07-01 00:00:00
abstract::The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000802
更新日期:2010-01-01 00:00:00
abstract::Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act) spliceosomes formed on site-specifically labeled pre-mRNA,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005539
更新日期:2015-09-22 00:00:00
abstract::Capsules allow bacteria to colonize novel environments, to withstand numerous stresses, and to resist antibiotics. Yet, even though genetic exchanges with other cells should be adaptive under such circumstances, it has been suggested that capsules lower the rates of homologous recombination and horizontal gene transfe...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007862
更新日期:2018-12-21 00:00:00
abstract::Cereal endosperm represents 60% of the calories consumed by human beings worldwide. In addition, cereals also serve as the primary feedstock for livestock. However, the regulatory mechanism of cereal endosperm and seed development is largely unknown. Polycomb complex has been shown to play a key role in the regulation...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003322
更新日期:2013-01-01 00:00:00
abstract::The ascomycete Trichoderma reesei is a highly prolific cellulase producer. While XYR1 (Xylanase regulator 1) has been firmly established to be the master activator of cellulase gene expression in T. reesei, its precise transcriptional activation mechanism remains poorly understood. In the present study, TrGAL11, a com...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008979
更新日期:2020-09-02 00:00:00
abstract::Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004228
更新日期:2014-04-17 00:00:00
abstract::The 2,2,7-trimethylguanosine (TMG) cap is one of the first identified modifications on eukaryotic RNAs. TMG, synthesized by the conserved Tgs1 enzyme, is abundantly present on snRNAs essential for pre-mRNA splicing. Results from ex vivo experiments in vertebrate cells suggested that TMG ensures nuclear localization of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009098
更新日期:2020-10-21 00:00:00
abstract::Evolutionary rescue occurs when a population that is threatened with extinction by an environmental change adapts to the change sufficiently rapidly to survive. Here we extend the mathematical theory of evolutionary rescue. In particular, we model evolutionary rescue to a sudden environmental change when adaptation in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004551
更新日期:2014-08-14 00:00:00
abstract::SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules, a SKN-1/Nrf function that is both well-known and conserved. Here we show th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002119
更新日期:2011-06-01 00:00:00
abstract::Sleep is a nearly universal behavior that is regulated by diverse environmental stimuli and physiological states. A defining feature of sleep is a homeostatic rebound following deprivation, where animals compensate for lost sleep by increasing sleep duration and/or sleep depth. The fruit fly, Drosophila melanogaster, ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008270
更新日期:2020-03-11 00:00:00
abstract::Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene express...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002789
更新日期:2012-06-01 00:00:00
abstract::Genome duplications are important evolutionary events that impact the rate and spectrum of beneficial mutations and thus the rate of adaptation. Laboratory evolution experiments initiated with haploid Saccharomyces cerevisiae cultures repeatedly experience whole-genome duplication (WGD). We report recurrent genome dup...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007396
更新日期:2018-05-25 00:00:00
abstract::Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To u...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1003394
更新日期:2013-03-01 00:00:00
abstract::The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020015
更新日期:2006-02-01 00:00:00
abstract::In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. Th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000455
更新日期:2009-04-01 00:00:00
abstract::DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukary...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003920
更新日期:2013-10-01 00:00:00