Biosystems, Journal Year: 2022, Volume and Issue: 213, P. 104631 - 104631
Published: Jan. 25, 2022
Language: Английский
European Heart Journal, Journal Year: 2022, Volume and Issue: 43(39), P. 3925 - 3946
Published: Aug. 18, 2022
This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance testing treating elevated levels, considers its inclusion global risk estimation. Epidemiologic genetic studies involving hundreds thousands individuals strongly support a causal continuous association between concentration outcomes different ethnicities; is factor even at very low levels low-density lipoprotein cholesterol. High associated with both microcalcification macrocalcification valve. Current findings do not as venous thrombotic events impaired fibrinolysis. Very may associate increased diabetes mellitus meriting further study. has pro-inflammatory pro-atherosclerotic properties, which partly relate to oxidized phospholipids carried by Lp(a). panel recommends least once adults; cascade potential value familial hypercholesterolaemia, or family personal history (very) high premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive management recommended, targeted according level. Lipoprotein apheresis an option progressive despite optimal factors. In conclusion, this reinforces outcomes. Trials treatments are critical confirm benefit stenosis.
Language: Английский
Citations
717
Nature, Journal Year: 2022, Volume and Issue: 610(7933), P. 704 - 712
Published: Oct. 12, 2022
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes
Language: Английский
Citations
503
Science, Journal Year: 2021, Volume and Issue: 373(6562), P. 1499 - 1505
Published: Sept. 23, 2021
Repeats associated with phenotype The degree to which repeated sequences within a genome affect human phenotypes has been difficult establish. Mukamel et al . examined thousands of genomes in the UK Biobank and found that some largest effects common genetic variants on phenotypes, including those clinical relevance, arise from protein-coding repeat polymorphisms (see Perspective by Gymrek Goren). Mapping size copy number these protein domains links variation lipoprotein(a) concentration, height, male pattern balding. Furthermore, alleles frequencies differ between individuals African European descent, resulting differences populations relevance for traits levels, risk factor coronary artery disease. —LMZ
Language: Английский
Citations
138
Atherosclerosis, Journal Year: 2022, Volume and Issue: 349, P. 17 - 35
Published: May 1, 2022
High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for cardiovascular disease. Lp(a) an enigmatic trait largely controlled by single gene (LPA) that contains a complex interplay several genetic elements with many surprising effects discussed in this review. A hypervariable coding copy number variation (the kringle IV type-2 repeat, KIV-2) generates >40 apolipoprotein(a) protein isoforms and determines median concentrations. Carriers small up to 22 domains have 5 times higher than those large (>22 domains). The effect apo(a) are, however, modified functional nucleotide polymorphisms (SNPs) distributed over complete range allele frequencies (<0.1% >20%) very pronounced on interaction is present between LPA SNPs, partially masking SNPs and, vice versa, lowering affected isoforms. This picture further complicated SNP-SNP interactions, poorly understood role other such as short tandem repeats linkage structures captured common R2 values. layer complexity derives from recent findings located KIV-2 repeat thus not accessible conventional sequencing genotyping technologies. critical impact ancestry correlation baseline values becomes increasingly evident.This review provides comprehensive overview architecture plasma, field has made tremendous progress introduction new Understanding genetics might be key mysteries booster ideas metabolism possible interventional targets.
Language: Английский
Citations
120
Journal of clinical lipidology, Journal Year: 2024, Volume and Issue: 18(3), P. e308 - e319
Published: April 1, 2024
Language: Английский
Citations
88
Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 535 - 549
Published: April 21, 2023
Language: Английский
Citations
75
Atherosclerosis, Journal Year: 2022, Volume and Issue: 349, P. 42 - 52
Published: May 1, 2022
Language: Английский
Citations
71
Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)
Published: Sept. 19, 2023
Abstract Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, structural characteristics of repeats. Besides, introduced diverse biological functions repeats reviewed existing methods for automatic repeat detection, classification, masking. Finally, analyzed type, structure, regulation human genome their role induction complex diseases. We believe that review will facilitate a comprehensive understanding provide guidance annotation in-depth exploration its association with
Language: Английский
Citations
69
Nature Genetics, Journal Year: 2023, Volume and Issue: 55(5), P. 768 - 776
Published: May 1, 2023
Abstract Genome-wide genealogies compactly represent the evolutionary history of a set genomes and inferring them from genetic data has potential to facilitate wide range analyses. We introduce method, ARG-Needle, for accurately biobank-scale sequencing or genotyping array data, as well strategies utilize perform association other complex trait use these methods build genome-wide using 337,464 UK Biobank individuals test across seven traits. Genealogy-based detects more rare ultra-rare signals ( N = 134, frequency 0.0007−0.1%) than genotype imputation ~65,000 sequenced haplotypes 64). In subset 138,039 exome samples, associations strongly tag (average r 0.72) underlying variants enriched (4.8×) loss-of-function variation. These results demonstrate that inferred may be leveraged in analysis traits, complementing approaches require availability large, population-specific panels.
Language: Английский
Citations
63
Nature, Journal Year: 2024, Volume and Issue: 627(8004), P. 604 - 611
Published: March 6, 2024
Abstract Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals with schizophrenia. Latent-factor analysis these data revealed that, whose more strongly expressed genes encoding synaptic components, astrocytes distinct functions for synthesizing cholesterol, an astrocyte-supplied component membranes. call this neuron astrocyte program (SNAP). In schizophrenia ageing—two conditions that involve declines cognitive flexibility plasticity 1,2 —cells divested from SNAP: astrocytes, glutamatergic (excitatory) GABAergic (inhibitory) all showed reduced SNAP expression corresponding degrees. The astrocytic neuronal components both involved which genetic risk factors were concentrated. SNAP, varies quantitatively even among similar age, may underlie many aspects normal interindividual differences be important point convergence multiple kinds pathophysiology.
Language: Английский
Citations
56