| 1. |
- Foo, Jia Nee, et al.
(författare)
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Coding Variants at Hexa-allelic Amino Acid 13 of HLA-DRB1 Explain Independent SNP Associations with Follicular Lymphoma Risk
- 2013
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 93:1, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 x 10(-15)). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 x 10(-14)). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.
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| 2. |
- Jia, Xiaoming, et al.
(författare)
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Cardiac magnetic resonance evaluation of the extent of myocardial injury in patients with inferior ST elevation myocardial infarction and concomitant ST depression in leads V1-V3 : Analysis from the MITOCARE Study
- 2018
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 140:3, s. 178-185
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study was to examine the pathophysiology of ST depression (STD) in leads V1-V3 in the setting of inferior ST elevation myocardial infarction (iSTEMI) through the perspective of cardiac magnetic resonance (CMR). Methods: Differences in myocardial area at risk (MaR), infarct size, ejection fraction and myocardial segment involvement by CMR were compared in MITOCARE trial patients with first iSTEMI with ST elevation (STE), STD or no ST changes (NST) in V1-V3. The frontal plane projection of the inferior wall MaR in relationship to the anterior/posterior chest wall was calculated and compared between groups. Results: Fifty-six patients were included. Patients with STD (n = 38) and STE (n = 5) in V1-V3 had significantly larger mean MaR compared to NST (n = 13; 32 ± 7%LV, 36 ± 10%LV and 26 ± 6%LV, respectively; p = 0.01). STD in leads V1-V3 was associated with more apical inferior and mid inferoseptal involvement and had a larger mean frontal plane projection of MaR compared with NST (24 ± 6%LV vs. 20 ± 6%LV, p = 0.04). Conclusion: STD in V1-V3 in iSTEMI is associated with larger MaR, more extension into the inferoseptal segments and likely results from greater frontal plane projection of the MaR, leading to reciprocal changes on the electrocardiogram.
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| 3. |
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| 4. |
- Jia, Xiaoming, et al.
(författare)
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Correlation of ST changes in leads V4–V6 to area of ischemia by CMR in inferior STEMI
- 2018
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 52:4, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- Objective. We aim to determine the correlation between ST-segment changes in leads V4–V6 and the extent of myocardial injury by cardiac magnetic resonance (CMR) in patients with inferior ST elevation (STE) myocardial infarction (iSTEMI). Design. Admission electrocardiogram and CMR data from the MITOCARE trial were used. Differences in mean myocardium at risk, infarct size, ejection fraction and myocardial segment involvement by CMR were compared in patients with first iSTEMI with STE, ST depression (STD) or no ST changes (NST) in V4–V6. Myocardial segment involvement was further evaluated by comparing proportion of patients in each group with ≥25% and ≥50% segment involvement. Results. Fifty-four patients were included. Patients with STE (n = 22) and STD (n = 16) in V4–V6 had significantly lower ejection fraction compared to NST (n = 16) (48% vs 48% vs 54%, p = .02). STE showed more apical, apical lateral and mid-inferolateral involvement but less basal inferior involvement than NST. STD exhibited greater basal inferoseptal involvement compared to STE. There were more patients with STE that had ≥25% and ≥50% apical lateral involvement compared with STD and NST groups. Patients with STD were more likely to have ≥25% and ≥50% basal inferoseptal involvement compared with STE and NST groups.Conclusion. Our study suggests that in iSTEMI, ST changes in the precordial leads V4–V6 correlates with greater myocardial injury and distribution of myocardium at risk.
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| 5. |
- Palmer, Duncan S., et al.
(författare)
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Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
- 2022
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 54:5, s. 541-547
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Tidskriftsartikel (refereegranskat)abstract
- We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
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