Browsing by Subject "Genetics"

Now showing 1 - 5 of 5
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    An African perspective on the genetic risk of chronic kidney disease: a systematic review
    (BioMed Central, 2018-10-19) George, Cindy; Yako, Yandiswa Y; Okpechi, Ikechi G; Matsha, Tandi E; Kaze Folefack, Francois J; Kengne, Andre P
    Background Individuals of African ethnicity are disproportionately burdened with chronic kidney disease (CKD). However, despite the genetic link, genetic association studies of CKD in African populations are lacking. Methods We conducted a systematic review to critically evaluate the existing studies on CKD genetic risk inferred by polymorphism(s) amongst African populations in Africa. The study followed the HuGE handbook and PRISMA protocol. We included studies reporting on the association of polymorphism(s) with prevalent CKD, end-stage renaldisease (ESRD) or CKD-associated traits. Given the very few studies investigating the effects of the same single nucleotide polymorphisms (SNPs) on CKD risk, a narrative synthesis of the evidence was conducted. Results A total of 30 polymorphisms in 11 genes were investigated for their association with CKD, ESRD or related traits, all using the candidate-gene approach. Of all the included genes, MYH9, AT1R and MTHFR genes failed to predict CKD or related traits, while variants in the APOL1, apoE, eNOS, XPD, XRCC1, renalase, ADIPOQ, and CCR2 genes were associated with CKD or other related traits. Two SNPs (rs73885319, rs60910145) and haplotypes (G-A-G; G1; G2) of the apolipoprotein L1 (APOL1) gene were studied in more than one population group, with similar association with prevalent CKD observed. The remaining polymorphisms were investigated in single studies. Conclusion According to this systematic review, there is currently insufficient evidence of the specific polymorphisms that poses African populations at an increased risk of CKD. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms, specific to African populations.
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    Community engagement strategies for genomic studies in Africa: a review of the literature
    (2015-04-12) Tindana, Paulina; de Vries, Jantina; Campbell, Megan; Littler, Katherine; Seeley, Janet; Marshall, Patricia; Troyer, Jennifer; Ogundipe, Morisola; Alibu, Vincent P; Yakubu, Aminu; Parker, Michael
    Background: Community engagement has been recognised as an important aspect of the ethical conduct of biomedical research, especially when research is focused on ethnically or culturally distinct populations. While this is a generally accepted tenet of biomedical research, it is unclear what components are necessary for effective community engagement, particularly in the context of genomic research in Africa. Methods: We conducted a review of the published literature to identify the community engagement strategies that can support the successful implementation of genomic studies in Africa. Our search strategy involved using online databases, Pubmed (National Library of Medicine), Medline and Google scholar. Search terms included a combination of the following: community engagement, community advisory boards, community consultation, community participation, effectiveness, genetic and genomic research, Africa, developing countries. Results: A total of 44 articles and 1 thesis were retrieved of which 38 met the selection criteria. Of these, 21 were primary studies on community engagement, while the rest were secondary reports on community engagement efforts in biomedical research studies. 34 related to biomedical research generally, while 4 were specific to genetic and genomic research in Africa. Conclusion: We concluded that there were several community engagement strategies that could support genomic studies in Africa. While many of the strategies could support the early stages of a research project such as the recruitment of research participants, further research is needed to identify effective strategies to engage research participants and their communities beyond the participant recruitment stage. Research is also needed to address how the views of local communities should be incorporated into future uses of human biological samples. Finally, studies evaluating the impact of CE on genetic research are lacking. Systematic evaluation of CE strategies is essential to determine the most effective models of CE for genetic and genomic research conducted in African settings.
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    Family Histories of Mental Illness and Violence in State Patients
    (2021) Vogts, Elizabeth; Roffey, M; Kaliski, Sean; Ramesar, S
    Background: It is known that both severe mental illness and violence have genetic components. Multiple genes play a role in the cause of violent behaviour. Violence is one of the leading causes of death for young people in South Africa and yet little is known about its prevalence in state patients and their family members. Aim: This study aimed to investigate the prevalence of violence and mental illness in the families of state patients, to what extend these coincide and to compare schizophrenia and mood psychosis in that context. Setting: The study included 60 state patients' folders, all of whom were diagnosed with a psychotic disorder, in accordance with DSM5 criteria. The subjects were divided into two groups: those who have committed violence and those who have not committed violence. Method: Patients' folders were selected by purposive sampling. These folders were then reviewed by the researcher and a questionnaire was completed. Results: Violent patients had more first-generation relatives with violent convictions (68.2%), compared to 36.4% of non-violent patients. Only 3.3% of non-violent patients witnessed domestic violence, whereas 13.3% of violent patients witnessed domestic violence. A significantly higher proportion of patients with bipolar disorder had been convicted of physical assault (p=0.035). 17.6% of violent schizophrenia patients had a family history of violence and mental illness, compared to 18.2% of violent patients with mood psychoses which is not statistically significant. Conclusion: It was found that violence runs in families and that mental illness and violence was prevalent in the described group. Of further concern was that more violent patients witnessed domestic violence compared to non-violent patients, emphasising the idea that the cause of violence is multifactorial (genetic, environmental), and that identification of not only high-risk patients but also high-risk families need to be implemented.
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    Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
    (2013) Davis, Lea K; Yu, Dongmei; Keenan, Clare L; Gamazon, Eric R; Konkashbaev, Anuar I; Derks, Eske M; Neale, Benjamin M; Yang, Jian; Lee, S Hong; Evans, Patrick; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, Oscar J; Bloch, Michael H; Blom, Rianne M; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond; Cappi, Carolina; Cardona Silgado, Julio C; Cath, Danielle C; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Conti, David V; Cook, Edwin H; Coric, Vladimir; Cullen, Bernadette A; Deforce, Dieter
    The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
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    Whole exome sequencing: a customised approach to exploring the genetic basis of musculoskeletal soft tissue injuries
    (2018) Gibbon, Andrea; September, Alison V; Collins, Malcolm
    Several DNA sequence variants have previously been associated with the risk of musculoskeletal soft tissue injuries, suggesting a role for genetics in the aetiology of common sporting injuries such as chronic Achilles tendinopathy (AT) and anterior cruciate ligament (ACL) ruptures. Genetic risk modifiers have primarily been identified using a hypothesis driven candidate gene approach. However, the ability to identify all risk-conferring variants using this approach alone is limited. Therefore, the primary aim of this thesis was to further define the molecular signatures of musculoskeletal soft tissue injuries mapping to specific genomic intervals encoding several structural and regulatory components of the extracellular matrix (ECM). Genes encoding the tenascin-C (TNC) glycoprotein (9q33.1) and the α1 chain of type XXVII collagen (COL27A1, 9q32), as well as matrix metallopeptidase 3 (MMP3, 11q22) and the α1 chain of type I collagen (COL1A1, 17q21.33), have previously been associated with the risk of injury and were therefore prioritised for further interrogation. Previously associated variants within these regions and/or new candidate variants identified by whole exome sequencing (WES) and prioritised through the application of a customised, tiered filtering strategy, were genotyped in several previously recruited, self-identified White Achilles tendon injury and ACL rupture cohorts. The second aim of this study was to determine whether the observed risk-associated signatures in the self-identified White cohorts were similar to those underpinning injury in an ancestrally admixed sample, using ACL ruptures in a South African Coloured cohort as the phenotypic model.