GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis DOI Creative Commons
Shuai Yuan, Jie Chen, Jiawei Geng

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 12, 2025

Abstract Sarcoidosis is a complex inflammatory disease with strong genetic component. Here, we perform genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide studies enrichment analyses explore pathways involved Mendelian randomization examine associations modifiable factors circulating biomarkers. 28 genomic sarcoidosis, the C1orf141-IL23R locus showing largest effect size. observe gene expression patterns related spleen, whole blood, lung, highlight 75 tissue-specific genes through studies. Furthermore, analysis establish key roles for T cell activation, leukocyte adhesion, cytokine production sarcoidosis. Additionally, find between genetically predicted body mass index, interleukin-23 receptor, eight proteins.

Язык: Английский

Pan-UK Biobank GWAS improves discovery, analysis of genetic architecture, and resolution into ancestry-enriched effects DOI Creative Commons
Konrad J. Karczewski, Rahul Gupta, Masahiro Kanai

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 15, 2024

Summary Large biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, individuals from diverse ancestry groups are often excluded analyses due to concerns about population structure introducing false positive associations. Here, we generate mixed model associations and meta-analyses across groups, inclusive a larger fraction UKB than previous efforts, produce freely-available summary statistics for 7,266 We build quality control analysis framework informed architecture. Overall, identify 14,676 significant loci (p < 5 x 10 -8 ) in meta-analysis were not found EUR group alone, including novel example between CAMK2D triglycerides. also highlight ancestry-enriched variation, known pleiotropic missense variant G6PD associated with several biomarker release these results publicly alongside FAQs describe caveats interpretation results, enhancing available resources risk variants populations.

Язык: Английский

Процитировано

66
‘All of Us’ genetics chart stirs unease over controversial depiction of race DOI

Max Kozlov

Nature, Год журнала: 2024, Номер unknown

Опубликована: Фев. 23, 2024

Язык: Английский

Процитировано

40
Calibrated prediction intervals for polygenic scores across diverse contexts DOI
Kangcheng Hou,

Ziqi Xu,

Yi Ding

и другие.

Nature Genetics, Год журнала: 2024, Номер 56(7), С. 1386 - 1396

Опубликована: Июнь 17, 2024

Язык: Английский

Процитировано

21
Long-read sequencing and structural variant characterization in 1,019 samples from the 1000 Genomes Project DOI Creative Commons
Siegfried Schloissnig, Samarendra Pani, Bernardo Rodríguez–Martín

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 20, 2024

Structural variants (SVs) contribute significantly to human genetic diversity and disease

Язык: Английский

Процитировано

15
Physical Activity and Incident Obesity Across the Spectrum of Genetic Risk for Obesity DOI Creative Commons
Evan L. Brittain, Lide Han, Jeffrey Annis

и другие.

JAMA Network Open, Год журнала: 2024, Номер 7(3), С. e243821 - e243821

Опубликована: Март 27, 2024

Importance Despite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic variability, increasing risk of obesity. Objective To use activity, clinical, and data from All Us Research Program (AoURP) explore association higher body mass index (BMI) with level physical needed reduce incident Design, Setting, Participants In this population–based retrospective cohort study, participants were enrolled AoURP between May 1, 2018, July 2022. Enrollees who European ancestry, owned a personal tracking device, did have up 6 months into included analysis. Exposure expressed as daily step counts polygenic score (PRS) BMI, calculated weight kilograms divided by height meters squared. Main Outcome Measures Incident (BMI ≥30). Results A total 3124 met inclusion criteria. Among 3051 available data, 2216 (73%) women, median age was 52.7 (IQR, 36.4-62.8) years. The walked 8326 6499-10 389) steps/d over 5.4 3.4-7.0) years tracking. incidence study period increased 13% (101 781) 43% (335 lowest highest PRS quartiles, respectively ( P = 1.0 × 10 −20 ). BMI demonstrated an 81% increase 3.57 ) while mean count reduction 5.30 −12 when comparing 75th 25th percentiles, respectively. Individuals percentile would need walk 2280 (95% CI, 1680-3310) more steps per day (11 020 total) than those at 50th comparable individuals PRS, baseline 22 additional 3460 steps/d; 24, 4430 26, 5380 28, 6350 steps/d. Conclusions Relevance across background quantified. Population-based may underestimate prevent among high risk.

Язык: Английский

Процитировано

13
Evolutionary history and biological adaptation of Han Chinese people on the Mongolian Plateau DOI Creative Commons
Xiangping Li, Mengge Wang, Haoran Su

и другие.

hLife, Год журнала: 2024, Номер 2(6), С. 296 - 313

Опубликована: Апрель 23, 2024

Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis adaptative traits or complex diseases. Recent ancient genome data allow us trace how key evolved in different human populations over time, connecting population history with disease susceptibility western Eurasians. To fill this gap eastern Eurasians provide deep insights into evolutionary population-specific biological traits, we explored one integrative modern genomic database, including 225 out 5583 genomes first reported here. We comprehensively characterized adaptation Han Chinese individuals on Mongolian Plateau based allele frequency spectrum haplotype-resolved fragments. found strong homogeneity among geographically from Inner Mongolia (IMH). reconstructed their admixture models events, revealing that IMH had a close relationship millet farmers obtained additional gene flow Altaic-speaking populations. The enrichment selected candidate genes suggested essential metabolism-related promoted rapid environmental shifts dietary changes during agricultural innovations. Evolutionary trajectory reconstruction methylenetetrahydrofolate reductase (MTHFR) fatty acid desaturase 1 (FADS1) Neolithic transition period differentiated metabolic rate folate acid. revealed polygenicity pleiotropy genes, indicating recent polygenic adaptations, interactions, genotype-phenotype correlations have contributed architecture

Язык: Английский

Процитировано

12
Seeing data as t-SNE and UMAP do DOI Creative Commons

Vivien Marx

Nature Methods, Год журнала: 2024, Номер 21(6), С. 930 - 933

Опубликована: Май 24, 2024

Dimension reduction helps to visualize high-dimensional datasets. These tools should be used thoughtfully and with tuned parameters. Sometimes, these methods take a second thought.

Язык: Английский

Процитировано

12
Analysis of gene expression in the postmortem brain of neurotypical Black Americans reveals contributions of genetic ancestry DOI Creative Commons
Kynon JM Benjamin, Qiang Chen, Nicholas J. Eagles

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(6), С. 1064 - 1074

Опубликована: Май 20, 2024

Abstract Ancestral differences in genomic variation affect the regulation of gene expression; however, most expression studies have been limited to European ancestry samples or adjusted identify ancestry-independent associations. Here, we instead examined impact genetic on and DNA methylation postmortem brain tissue admixed Black American neurotypical individuals ancestry-dependent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts networks, while notably not implicating neurons, are enriched for related immune response vascular explain up 26% heritability ischemic stroke, 27% Parkinson disease 30% Alzheimer’s disease. DEGs also show general enrichment diverse immune-related traits but depletion psychiatric-related traits. We compared non-Hispanic white Americans, confirming ancestry-associated DEGs. Our results delineate extent which affects human implications illness risk.

Язык: Английский

Процитировано

10
Deep learning of left atrial structure and function provides link to atrial fibrillation risk DOI Creative Commons
James P. Pirruccello, Paolo Di Achille, Seung Hoan Choi

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 21, 2024

Abstract Increased left atrial volume and decreased function have long been associated with fibrillation. The availability of large-scale cardiac magnetic resonance imaging data paired genetic provides a unique opportunity to assess the contributions structure function, understand their relationship risk for Here, we use deep learning surface reconstruction models measure minimum volume, maximum stroke emptying fraction in 40,558 UK Biobank participants. In genome-wide association study 35,049 participants without pre-existing cardiovascular disease, identify 20 common loci function. We find that polygenic increased are fibrillation its downstream consequences, including stroke. Through Mendelian randomization, evidence supporting causal role enlargement dysfunction on risk.

Язык: Английский

Процитировано

10
Gene-environment interactions within a precision environmental health framework DOI Creative Commons
Alison A. Motsinger‐Reif, David M. Reif, Farida S. Akhtari

и другие.

Cell Genomics, Год журнала: 2024, Номер 4(7), С. 100591 - 100591

Опубликована: Июнь 25, 2024

Understanding the complex interplay of genetic and environmental factors in disease etiology role gene-environment interactions (GEIs) across human development stages is important. We review state GEI research, including challenges measuring advantages analysis understanding mechanisms. discuss evolution studies from candidate to genome-wide interaction (GWISs) multi-omics mediating effects. advancements methods importance large-scale datasets. also address translation findings into precision health (PEH), showcasing real-world applications healthcare prevention. Additionally, we highlight societal considerations justice, return results participants, data privacy. Overall, underscore significance for prediction prevention advocate integrating exposome PEH omics studies.

Язык: Английский

Процитировано

10