Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

He, Jiangjiang; Lin, Haijiang; Ding, Yingying; Liu, Xing; Xu, Kelin; Chen, Xiaoxiao; Shen, Weiwei; Zhou, Shao-Lai; Wang, Miaochen; Xia, Jingjing; He, Na

doi:10.1186/s12967-022-03817-6

Cited by 3 publications

(1 citation statement)

References 64 publications

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“…Genomic DNA, extracted from whole peripheral blood samples using a commercial DNA extraction kit (QIAamp DNA Blood Kits; Qiagen, Hilden, Germany) and quantified using PicoGreen reagent (PicoGreen dsDNA Quantitation Reagent; Invitrogen, Carlsbad, California, USA), was genotyped on the Infinium Chinese Genotyping Array-24 v1.0 BeadChip (727 349 SNPs) [ 18 ]. SNPs and individuals used in the GWAS were selected according to the following criteria: individual call rate more than 95%, SNP call rate more than 95%, minor allele frequencies at least 0.05, and Hardy--Weinberg equilibrium at least 1 × 10 −6 .…”

Section: Methodsmentioning

confidence: 99%

Differential genome-wide associated variants and enriched pathways of electrocardiogram parameters among people with versus without HIV

Ding

Lin

et al. 2023

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Objectives: People with HIV (PWH) are more likely to develop electrocardiogram (ECG) abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes and enriched pathways of ECG parameters among PWH and HIV-negative controls. Design: A cross-sectional study. Method: We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH (n = 1730) and HIV-negative controls (n = 3746). Genome-wide interaction analyses were also conducted. Results: A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2, eleven for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD, and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes (SCN5A, CNOT1). Genetic variants had a significant interaction with HIV infection (P < 5 × 10−8), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex. Conclusion: The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production and latency among PWH.

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Section: Methodsmentioning

confidence: 99%

Differential genome-wide associated variants and enriched pathways of electrocardiogram parameters among people with versus without HIV

Ding

Lin

et al. 2023

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Genomic adaptation to small population size and saltwater consumption in the critically endangered Cat Ba langur

Zhang,

Leonard,

Passaro

et al. 2024

Nat Commun

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Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam’s famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.

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Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment

Pan

Zhang

et al. 2023

Circulation Research

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Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.

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Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

Cited by 3 publications

References 64 publications

Differential genome-wide associated variants and enriched pathways of electrocardiogram parameters among people with versus without HIV

Differential genome-wide associated variants and enriched pathways of electrocardiogram parameters among people with versus without HIV

Genomic adaptation to small population size and saltwater consumption in the critically endangered Cat Ba langur

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment

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