Abstract:
:Evidence of the effects of genetic risk score (GRS) on secondary prevention is scarce and mixed. We investigated whether coronary artery disease (CAD) susceptible loci can be used to predict the risk of major adverse cardiovascular events (MACEs) in a cohort with acute coronary syndromes (ACSs). A total of 1667 patients hospitalized with ACS were enrolled and prospectively followed for a median of 2 years. We constructed a weighted GRS comprising 79 CAD risk variants and investigated the association between GRS and MACE using a multivariable cox proportional hazard regression model. The incremental value of adding GRS into the prediction model was assessed by integrated discrimination improvement (IDI) and decision curve analysis (DCA). In the age- and sex-adjusted model, each increase in standard deviation in the GRS was associated with a 33% increased risk of MACE (hazard ratio: 1.33; 95% confidence interval: 1.10-1.61; P = 0.003), with this association not attenuating after further adjustment for traditional cardiovascular risk factors. The addition of GRS to a prediction model of seven clinical risk factors and EPICOR prognostic model slightly improved risk stratification for MACE as calculated by IDI (+1.7%, P = 0.006; +0.3%, P = 0.024, respectively). DCA demonstrated positive net benefits by adding GRS to other models. GRS was associated with MACE after multivariable adjustment in a cohort comprising Chinese ACS patients. Future studies are needed to validate our results and further evaluate the predictive value of GRS in secondary prevention.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Jiang J,Zheng Q,Han Y,Qiao S,Chen J,Yuan Z,Yu B,Ge L,Jia J,Gong Y,Wang Z,Chen D,Zhang Y,Huo Ydoi
10.1093/hmg/ddaa025subject
Has Abstractpub_date
2020-04-15 00:00:00pages
1044-1053issue
6eissn
0964-6906issn
1460-2083pii
5739259journal_volume
29pub_type
杂志文章abstract::Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz110
更新日期:2019-09-15 00:00:00
abstract::The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.5.525
更新日期:1993-05-01 00:00:00
abstract::Familial infantile myasthenia is an autosomal recessive disorder, recently classified as congenital myasthenic syndrome type Ia. Onset of symptoms is at birth to early childhood with significant myasthenic weakness and possible respiratory distress, followed later in life by symptoms of mild to moderate myasthenia. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.4.635
更新日期:1997-04-01 00:00:00
abstract::Ketosis-prone diabetes (KPD) is a rare form of type 2 diabetes, mostly observed in subjects of west African origin (west Africans and African-Americans), characterized by fulminant and phasic insulin dependence, but lacking markers of autoimmunity observed in type 1 diabetes. PAX4 is a transcription factor essential f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh341
更新日期:2004-12-15 00:00:00
abstract::Prion diseases encompass a diverse group of neurodegenerative conditions characterized by the accumulation of misfolded prion protein (PrP) isoforms. Other conformational variants of PrP have also been proposed to contribute to neurotoxicity in prion diseases, including misfolded intermediates as well as cytosolic and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt276
更新日期:2013-11-01 00:00:00
abstract::Cornelia de Lange syndrome (CdLS), which is reported to affect ∼1 in 10 000 to 30 000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition. CdLS can result from mutations in at least five ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy329
更新日期:2019-01-01 00:00:00
abstract::Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq453
更新日期:2011-01-01 00:00:00
abstract::Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn386
更新日期:2009-02-15 00:00:00
abstract::HTRA2-BETA1 is an SR-like protein that regulates alternative splice site selection in a concentration-dependent manner. Its proper concentration is important as several pathological states are associated with its change. We investigated the mechanism that controls the cellular HTRA2-BETA1 concentration and found it ut...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh051
更新日期:2004-03-01 00:00:00
abstract::We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.G...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu740
更新日期:2015-04-15 00:00:00
abstract::Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7), an enzyme involved in synthesizing the glycosaminoglycan linkage region of proteoglycans, is associated with the progeroid form of Ehlers-Danlos syndrome (EDS). In the invertebrates Drosophila melanogaster and Caenorhabditis elegans, mutations in beta4Ga...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm372
更新日期:2008-04-01 00:00:00
abstract::X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to use as a model in the testing of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr512
更新日期:2012-02-15 00:00:00
abstract::The hippocampus has a highly ordered structure and is composed of distinct layers. Neuronal migration is an essential part of the process of the layer formation because neurons are primarily generated near the ventricle and must migrate to arrive at their final locations during brain development. Impairment of brain d...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr194
更新日期:2011-07-15 00:00:00
abstract::Emerging evidence implicates epigenetic mechanisms in the pathogenesis of rheumatoid arthritis (RA). In this study, we have investigated the role of histone deacetylase (HDAC) enzymes in RA synovial fibroblasts (RASFs), a key cellular mediator of cartilage and bone destruction and determined effects of HDAC1 inhibitio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv258
更新日期:2015-10-01 00:00:00
abstract::A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial group...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.5.899
更新日期:1999-05-01 00:00:00
abstract::Huntington's disease (HD) is caused by the expansion mutation above a length threshold of a polyglutamine (polyQ) stretch in the huntingtin (Htt) protein. Mutant Htt (mHtt) pathogenicity is proposed to rely on its malfunction and propensity to misfold and aggregate. Htt has scaffolding properties and has been reported...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr178
更新日期:2011-07-15 00:00:00
abstract::Lysosomal neuraminidase (sialidase) occurs in a high molecular weight complex with the glycosidase beta-galactosidase and the serine carboxypeptidase protective protein/cathepsin A (PPCA). Association of the enzyme with PPCA is crucial for its correct targeting and lysosomal activation. In man two genetically distinct...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.2.313
更新日期:1998-02-01 00:00:00
abstract::Mutations that affect calcium homeostasis (Ca(2+)) in rod photoreceptors are linked to retinal degeneration and visual disorders such as retinitis pigmentosa and congenital stationary night blindness (CSNB). It is thought that the concentration of Ca(2+) in rod outer segments is controlled by a dynamic balance between...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv319
更新日期:2015-10-15 00:00:00
abstract::By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by inter...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.21.2329
更新日期:2001-10-01 00:00:00
abstract::Peripheral sensory perception is established through an elaborate network of specialized neurons that mediate the translation of extraorganismal stimuli through the use of a broad array of receptors and downstream effector molecules. Studies of human genetic disorders, as well as mouse and other animal models, have id...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddp412
更新日期:2009-10-15 00:00:00
abstract::DiGeorge syndrome, and more widely the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. A critical region of 500 kb has been delimited within which maps the breakpoint of a balanced translocation associated with mild CATCH 22 phenotypes. We report the isolation from this critical re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.5.633
更新日期:1996-05-01 00:00:00
abstract::Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg270
更新日期:2003-10-15 00:00:00
abstract::Mitochondrial dysfunction plays an important role in the etiology of neurodegenerative diseases. However, the progressive nature of neuronal loss in genetic models of mitochondrial dysfunction suggests the presence of compensatory mechanisms promoting neuronal survival under these conditions. Here, we identified the e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds500
更新日期:2013-03-01 00:00:00
abstract::Cilia are evolutionarily conserved organelles endowed with essential physiological and developmental functions. In humans, disruption of cilia motility or signaling leads to complex pleiotropic genetic disorders called ciliopathies. Cilia motility requires the assembly of multi-subunit motile components such as dynein...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt445
更新日期:2014-02-01 00:00:00
abstract::Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv183
更新日期:2015-08-15 00:00:00
abstract::DNA replication is a critical step for cells because of the propensity of replication forks to stall, as a consequence either of endogenous DNA damage or of the propensity of repeated sequences to form tertiary structures, which can impede fork progression. Moreover, as a result of stalled replication fork processing,...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/11.20.2447
更新日期:2002-10-01 00:00:00
abstract::Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq043
更新日期:2010-05-01 00:00:00
abstract::Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is the major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. However, the cellular function of the C9ORF72 protein remains unknown. Here, we demonstrate that C9ORF72 regulate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu068
更新日期:2014-07-01 00:00:00
abstract::Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz300
更新日期:2020-02-01 00:00:00
abstract::Schizophrenia is a severely debilitating psychiatric disease that is hypothesized to have its roots in neurodevelopment. Although the precise neuropathology underlying schizophrenia has remained elusive, there are consistent reports of abnormalities in several brain areas. Chief among these is the hippocampus, an area...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp266
更新日期:2009-09-01 00:00:00