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Mashup Score: 4
Background Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter. Methods We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia. Results In Europeans, higher genetically predicted TSAT increased genetic liabil
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Mashup Score: 0Evidence of a genetic background predisposing to complex regional pain syndrome type 1 - 7 month(s) ago
Background Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition. Methods Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n = 34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n = 50). Gene expression of peripheral blood macrophages was assessed. Results In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289
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Mashup Score: 4Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel - 9 month(s) ago
Background Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. Methods We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. Results In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PR
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Mashup Score: 0Online First | Journal of Medical Genetics - 3 year(s) ago
August 16, 2021 Genome-wide studies Myasthenia gravis genome-wide association study implicates AGRN as a risk locus , Zoi Zagoriti, Alyssa Camille Flint, Melanie Belle Martinez, Zhiyu Yang, Fotis Tsetsos, Yiolanda-Panayiota Christou, George Lagoumintzis, Evangelia Yannaki, Eleni Zamba-Papanicolaou, John Tzartos, Xanthippi Tsekmekidou, Kalliopi Kotsa, Efstratios…
Source: jmg.bmj.comCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
🚀 First on #MarchManuscriptChallenge: ▶️ Iron and risk of Dementia using @uk_biobank 👉 Higher TSAT associated with increased genetic liability to non-Alzheimer’s dementia: https://t.co/4ODa4H3YPI👀 💪 🧑🏿🤝🧑🏼@NIHAging, @uniofexeHLS @ExeterMed @lcpilling and team https://t.co/KbiPs3ayCt