ORCID Profile
0000-0002-4079-7494
Current Organisation
University of Pittsburgh
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Publisher: Springer Science and Business Media LLC
Date: 26-08-2021
DOI: 10.1186/S13073-021-00917-8
Abstract: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. The study s le was comprised of 7988 in iduals of erse ancestry. Common-variant and pathway analyses included an additional 13,257 in iduals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap. We identified a multi-ethnic set-based rare-variant association ( p = 3.48 × 10 −8 ) on chromosome X with ARMCX3 . Additional rare-variant associations include ARMCX3-AS1 , MRPS33 , and C16orf90 . Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A -mediated hypoxic response.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2021
DOI: 10.1038/S41366-021-00817-2
Abstract: Neck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference. We conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) in iduals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis. We identified rs227724 near the Noggin ( NOG) gene as a possible quantitative locus for neck circumference in men ( N = 8831, P = 1.74 × 10 −9 ) but not in women ( P = 0.08). The association was replicated in men ( N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis ( N = 15090, P = 2.94 × 10 −7 replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 ( PDZRN3 ) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins. Our study suggests that neck circumference may have unique genetic basis independent of BMI.
Publisher: Springer Science and Business Media LLC
Date: 03-2023
DOI: 10.1038/S41588-023-01314-0
Abstract: Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. In idual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2023
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2019
DOI: 10.1101/652966
Abstract: Sleep-disordered breathing (SDB) is a common disorder associated with significant morbidity. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program we report the first whole-genome sequence analysis of SDB. We identified 4 rare gene-based associations with SDB traits in 7,988 in iduals of erse ancestry and 4 replicated common variant associations with inclusion of additional s les (n=13,257). We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10 −8 ) on chromosome X with ARMCX3 . Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Results highlighted associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis and HIF1A -mediated hypoxic response.
Publisher: Oxford University Press (OUP)
Date: 09-10-2020
Abstract: Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n = 2868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100 000 in iduals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2021
Publisher: Springer Science and Business Media LLC
Date: 09-12-2021
Publisher: Elsevier BV
Date: 11-2019
Publisher: American Thoracic Society
Date: 15-11-2022
Publisher: Public Library of Science (PLoS)
Date: 16-04-2019
Location: Korea, Republic of
Location: United States of America
No related grants have been discovered for Jiwon Lee.