| 1. |
- Bonham, LW, et al.
(författare)
-
Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
-
Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
|
|
| 2. |
|
|
| 3. |
- Gao, YX, et al.
(författare)
-
Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
-
Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
|
|
| 4. |
|
|
| 5. |
- Karaye, Kamilu M., et al.
(författare)
-
Incidence, clinical characteristics, and risk factors of peripartum cardiomyopathy in Nigeria : results from the PEACE Registry
- 2020
-
Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 7:1, s. 236-244
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to describe the incidence, clinical characteristics and risk factors of peripartum cardiomyopathy (PPCM) in Nigeria.Methods and Results: The study was conducted in 22 hospitals in Nigeria, and PPCM patients were consecutively recruited between June 2017 and March 2018. To determine factors associated with PPCM, the patients were compared with apparently healthy women who recently delivered, as controls. Four hundred six patients were compared with 99 controls. The incidence and disease burden (based on the rate of consecutive recruitment of subjects) varied widely between the six geographical zones of Nigeria. From the North-West zone, 72.3% of the patients was recruited, where an incidence as high as 1 per 96 live births was obtained in a centre, while the disease was uncommon (7.6% of all recruited patients) in the South. Majority of the patients (76.6%) and controls (74.8%) (p = 0.694) were of Hausa-Fulani ethnic group. Atrial fibrillation, intracardiac thrombus, stroke, and right ventricular systolic dysfunction were found in 1.7%, 6.4%, 2.2%, and 54.9% of the patients, respectively. Lack of formal education (odds ratio [OR] 3.08, 95% confidence interval [1.71, 5.53]; P < 0.001), unemployment (OR: 3.28 [2.05, 5.24]; P < 0.001), underweight (OR: 13.43 [4.17, 43.21]; P < 0.001) and history of pre-eclampsia (OR: 9.01 [2.18, 37.75]; P = 0.002) emerged as independent PPCM risk factors using regression models. Customary hot baths (OR: 1.24 [0.80, 1.93]; P = 0.344), pap enriched with dried lake salt (OR: 1.20 [0.74, 1.94]; P = 0.451), and Hausa-Fulani ethnicity (OR: 1.11 [0.67, 1.84]; P = 0.698) did not achieve significance as PPCM risk factors.Conclusions: In Nigeria, the burden of PPCM was greatest in the North-West zone, which has the highest known incidence. PPCM was predicted by sociodemographic factors and pre-eclampsia, which should be considered in its control at population level. Postpartum customary birth practices and Hausa-Fulani ethnicity were not associated with PPCM in Nigeria.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Ferrari, Raffaele, et al.
(författare)
-
Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
-
Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
|
|
