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Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents
Jansen van Rensburg, Danielle. 2024. Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/e75a9276-9a36-473b-a6b5-6d2fca1357c6
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867614110480334848 |
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| access_status_str | Open Access |
| author | Jansen van Rensburg, Danielle |
| author2 | Hemmings, Sian Megan Joanna |
| author_browse | Hemmings, Sian Megan Joanna Jansen van Rensburg, Danielle |
| author_facet | Hemmings, Sian Megan Joanna Jansen van Rensburg, Danielle |
| author_sort | Jansen van Rensburg, Danielle |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Jansen van Rensburg, Danielle. 2024. Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/e75a9276-9a36-473b-a6b5-6d2fca1357c6 |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/129362 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:46:49.940Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/129362 Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents Jansen van Rensburg, Danielle Hemmings, Sian Megan Joanna Womersley, Jacqueline Samantha Swart, Patricia Cathryn Seedat, Soraya Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Anxiety in adolescence -- Genetic aspects -- South Africa MicroRNA -- South Africa Anxiety sensitivity -- South Africa Epigenetics -- South Africa UCTD Jansen van Rensburg, Danielle. 2024. Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents. Unpublished masters dissertation. Stellenbosch : Stellenbosch University [online]. Available at: https://scholar.sun.ac.za/items/e75a9276-9a36-473b-a6b5-6d2fca1357c6 Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: Anxiety proneness (AP) is the tendency to react fearfully to stressors due to the belief that such stressors have harmful consequences. Anxiety proneness is a risk factor for the development of anxiety disorders. The biological mechanisms underlying AP remain unclear, although its aetiology includes both genetic and environmental factors. Epigenetic mechanisms, such as microRNAs (small, non-coding RNAs 19-20 nucleotides long), may explain how the combination of genetic variation and environmental risk factors (e.g., childhood trauma (CT)), can increase the risk of developing anxiety disorders. This study aimed to investigate AP-associated differences in microRNA expression using whole blood obtained from South African adolescents with variable exposure to CT. This study is a sub-study of a larger parent study that aimed to investigate the effects of low and high AP and CT on both neuropsychological performance and emotional processing in adolescents. South African adolescents were recruited from four educational districts in Cape Town, South Africa. Anxiety proneness was assessed using a composite score reflecting trait anxiety and anxiety sensitivity. Childhood trauma exposure was determined using the Childhood Trauma Questionnaire. For the current sub-study, 94 participants were grouped as either low-/high- AP and low-/high- CT, based on scores obtained in the parent study. Most participants were female (75.86%) with an average age of 15 years (SD = 1.20). Total RNA was extracted from whole blood samples stored in PAXgene tubes using the PAXgene Blood miRNA Kit. High quality total RNA (n = 88) was sent for microRNA-sequencing. Differential microRNA expression analysis was conducted with DESeq2 in R. Target prediction analysis was performed using TargetScan and DIANA-microT. For KEGG pathway analysis, the DIANA mirPATH tool was used, where only significant (p < 0.05) pathways were included. hsa-miR-28-5p was found to be upregulated in individuals with high AP and hsa-miR-502-3p and hsa-miR-500a-3p downregulated in individuals with high levels of AP, irrespective of CT. Pathway analysis, based on predicted and overlapping mRNA targets, revealed four pathways, including amphetamine addiction, dopamine synapse, nicotine addiction, and long-term potentiation, that were associated with high levels of AP. To our knowledge, this is the first study to find a link between hsa-miR-28-5p, hsa-miR-500a-3p and hsa-miR-502-3p, and AP in a cohort of South African adolescents. Based on potential target genes (GRIN2B, GRIA1, GRIA2, GRIA4, PPP3CA and PPP3CC), these results suggest a correlation between AP and calcineurin and glutamate signalling. Future studies could benefit from repeating this study in order to verify the differentially expressed miRNAs identified in high-AP participants. AFRIKAANSE OPSOMMING: Angsgeneigdheid (AG) is die neiging om angstig op stressore te reageer as gevolg van die oortuiging dat die stressore skadelike gevolge het. Angstigheid is ‘n risikofaktor vir die ontwikkeling van angsversteurings. Die biologiese meganismes onderliggend aan AG bly onduidelik, alhoewel die etiologie daarvan beide genetiese- en omgewingsfaktore insluit. Epigenetiese meganismes, soos mikroRNS’e (klein, nie-koderende RNS’e wat 19-20 nukleotiedes lank is), kan verduidelik hoe die kombinasie van genetiese variasie en omgewingsrisikosfaktore (byvoorbeeld trauma in kinderjare (TK)), die risiko kan verhoog om angsversteurings te ontwikkel. Hierdie studie het ten doel gehad om AG-geassosieerde verskille in mikroRNS uitdrukking te ondersoek deur gebruik te maak van volbloed verkry van Suid-Afrikaanse tieners met varieerende blootstelling aan TK. Hierdie studie is ‘n substudie van ‘n groter moederstudie wat daarop gemik was om die uitwerkking van lae en hoë AG en TK op beide neuropsigologiese optrede, en die emosionele prosessering by tieners te ondersoek. Suid-Afrikaanse tieners is uit vier opvoedkundige distrikte in Kaapstad, SuidAfrika, gewerf. Angsgeneigdheid is geassesseer deur gebruik te maak van ‘n saamgestelde telling wat angs en angs sensitiwiteit weerspieël. Kindertrauma-blootstelling is met behulp van die Kinderjare Trauma-vraelys bepaal. Vir hierdie substudie is 94 deelnemers volgens hul vraelystellings gegroepeer as óf lae-/hoë-AG en lae-/hoë-KT, gebasseer op tellings wat in die moederstudie verkry is. Die meerderheid deelnemers was vroulik (75.86%) met ‘n gemiddelde ouderdom van 15 jaar (SD = 1.20). Totale RNS is onttrek vanuit volbloedmonsters met behulp van die PAXgene Blood miRNA Kit, waar dit in PAXgene-buise gestoor was. Hoë kwaliteit RNS (n = 88) is gestuur vir mikroRNS-volgordebepaling. Differensiële mikroRNS uitdrukking analise is uitgevoer met DESeq2 in R. Teiken voorspelling analise is uitgevoer met behulp van TargetScan en DIANA-mikroT. Vir KEGG-roete-analise is die DIANA mirPATH-instrument gebruik, waar slegs betekenisvolle (p < 0.05) paaie ingesluit is. Daar is gevind dat hsa-miR-28-5p opgereguleer is in individue met hoë vlakke van AG en hsa-miR502-3p en hsa-miR-500a-3p afgereguleer is in individue met hoë vlakke van AG, ongeag van TK ervaring. Roete analise was gebasseer op voorspelde en oorvleuelende bRNS-teikens, het vier roetes aan die lig gebring, insluitend amfetamienverslawing, dopamien-sinaps, nikotienverslawing en langtermynpotensiëring wat geassosieer is met hoë vlakke van AG. Na ons wete is dit die eerste studie wat 'n verband tussen hsa-miR-28-5p, hsa-miR-500a-3p en hsa-miR-502-3p en AG in 'n groep Suid-Afrikaanse tieners gevind het. Gebasseer op potensiële teikengene (GRIN2B, GRIA1, GRIA2, GRIA4, PPP3CA en PPP3CC), dui hierdie resultate op 'n korrelasie tussen AG en kalsineurien en glutamaat sein. Toekomstige studies kan baat vind by die herhaling van hierdie studie om die differensiële mikroRNSe wat in hoë-AG deelnemers geïdentifiseer is, te verifieer. Masters 2023-11-17T09:21:56Z 2024-02-20T08:54:10Z 2023-11-17T09:21:56Z 2024-02-20T08:54:10Z 2023-11 Thesis https://scholar.sun.ac.za/handle/10019.1/129362 en Stellenbosch University xvi, 109 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Anxiety in adolescence -- Genetic aspects -- South Africa MicroRNA -- South Africa Anxiety sensitivity -- South Africa Epigenetics -- South Africa UCTD Jansen van Rensburg, Danielle Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title | Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title_full | Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title_fullStr | Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title_full_unstemmed | Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title_short | Identifying microRNAs associated with anxiety proneness in a cohort of South African adolescents |
| title_sort | identifying micrornas associated with anxiety proneness in a cohort of south african adolescents |
| topic | Anxiety in adolescence -- Genetic aspects -- South Africa MicroRNA -- South Africa Anxiety sensitivity -- South Africa Epigenetics -- South Africa UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/129362 |
| work_keys_str_mv | AT jansenvanrensburgdanielle identifyingmicrornasassociatedwithanxietypronenessinacohortofsouthafricanadolescents |