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  • Avery, Daniel  (3)
  • Bennett, Derrick  (3)
  • Chen, Biyun  (3)
  • Chen, Xiaofang  (3)
  • China Kadoorie Biobank Collaborative Group  (3)
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  • 1
    Online Resource
    Online Resource
    Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese Adults
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. 11 ( 2019-11-01), p. 2155-2164
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. 11 ( 2019-11-01), p. 2155-2164
    Abstract: In observational studies, type 2 diabetes is associated with two- to fourfold higher risk of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank (CKB), we examined associations of genetically predicted type 2 diabetes with CVD among ∼160,000 participants to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (odds ratio 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n = 6,819) and elevated risk of ischemic stroke (IS) (1.08 [1.02, 1.14] ; n = 17,097), nonlacunar IS (1.09 [1.03, 1.16]; n = 13,924), and major coronary event (1.12 [1.02, 1.23] ; n = 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n = 3,173) or intracerebral hemorrhage (ICH) (1.01 [0.94, 1.10] , n = 6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (P for heterogeneity & gt;0.3) and with the associations of type 2 diabetes with IS, ICH, and coronary heart disease in two-sample Mendelian randomization analyses based on summary statistics from European population genome-wide association studies (P for heterogeneity & gt;0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-0224
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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    Online Resource
  • 2
    Online Resource
    Online Resource
    PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations
    Oxford University Press (OUP) ; 2024
    In:  European Journal of Preventive Cardiology ( 2024-01-10)
    Details
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), ( 2024-01-10)
    Abstract: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. Methods and results In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45–0.83); P = 0.0015] , major occlusive vascular events [n = 15 752; 0.80 (0.67–0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66–0.98); P = 0.029] . However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08–1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71–7.60); P = 7.3 × 10−4] . We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38–2.54); P = 5.4 × 10−5] and self-reported asthma [pooled OR of 1.17 (1.04–1.30); P = 0.0071] . There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. Conclusion The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. Lay summary Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    URL: Article
    DOI: 10.1093/eurjpc/zwae009
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2646239-4
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  • 3
    Online Resource
    Online Resource
    Alcohol consumption and risks of more than 200 diseases in Chinese men
    Springer Science and Business Media LLC ; 2023
    In:  Nature Medicine Vol. 29, No. 6 ( 2023-06), p. 1476-1486
    Details
    In: Nature Medicine, Springer Science and Business Media LLC, Vol. 29, No. 6 ( 2023-06), p. 1476-1486
    Abstract: Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of 〉 512,000 adults (41% men), including 168,050 genotyped for ALDH2 - rs671 and ADH1B - rs1229984 , with 〉 1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Among men, alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related, such as cataract ( n  = 2,028; hazard ratio 1.21; 95% confidence interval 1.09–1.33, per 280 g per week) and gout ( n  = 402; 1.57, 1.33–1.86). Genotype-predicted mean alcohol intake was positively associated with established ( n  = 28,564; 1.14, 1.09–1.20) and new alcohol-associated ( n  = 16,138; 1.06, 1.01–1.12) diseases, and with specific diseases such as liver cirrhosis ( n  = 499; 2.30, 1.58–3.35), stroke ( n  = 12,176; 1.38, 1.27–1.49) and gout ( n  = 338; 2.33, 1.49–3.62), but not ischemic heart disease ( n  = 8,408; 1.04, 0.94–1.14). Among women, 2% drank alcohol resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects. Among Chinese men, alcohol consumption increased multiple disease risks, highlighting the need to strengthen preventive measures to reduce alcohol intake.
    Type of Medium: Online Resource
    ISSN: 1078-8956 , 1546-170X
    URL: Article
    DOI: 10.1038/s41591-023-02383-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1484517-9
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