Exploring the links between urban agriculture, land use and food security in the Philippi Horticultural Area (PHA)

Magister Artium - MAHunger is more than just a feeling, it is the lack of access to safe nutritious food, which in turn may result in anger towards government, low performance, sadness and a limited will to survive. Urban agriculture has been identified as a source of livelihood for many urban residents and could fundamentally change food insecure cities like Cape Town. The Philippi Horticultural Area (PHA) is one such place with an enormous amount of potential to assist the City of Cape Town (CCT) to overcome food insecurity challenges. The PHA is the focus of this thesis that aims to determine the impacts that housing and industrial developments in the PHA have had, and might have in the future, on food security in the Greater Cape Town Area (GCTA). The specific objectives of the study are as follows: (1) To investigate the urban agricultural distribution of the PHA; (2) to investigate agricultural facilitation, people empowerment and the use of land for agricultural purposes; (3) To determine the level of access to food for people within and around the PHA; and (4) To examine the links between the urban agricultural food sector and food production. Mixed method research was employed, hinging on the Sustainable Livelihoods Approach (SLA) as the conceptual framework. Snowball sampling was used to select 68 participants who were interviewed. One key finding of the study showed that the PHA had a significant value to the participants, many of whom called the place ‘home’. Another finding is that urban agriculture provides fresh food produce to many local residents. In-depth discussions with officials and farmers, both commercial and small-scale farmers in the PHA, revealed that the PHA is a valuable portion of farmland, and contributes significantly towards food security in and around the PHA. With the use of the SLA as the conceptual framework, the study contributes towards other livelihood outcomes dependant on urban agriculture to improve access, availability and stability of food security within the PHA. Although urban agriculture is a minimal contributor to food security in the PHA, there are other benefits enjoyed by low-income communities such as food aid given by farmers to assist low-income housing communities, educational opportunities to enhance small growers in the PHA, small-scale community garden outreach and employment

Trauma related drinking to cope: A phenotypic and molecular genetic investigation of the self-medication model

Posttraumatic stress disorder (PTSD) and alcohol use problems (AUP) commonly co-occur, have shared latent genetic risk, and are associated with many negative public health outcomes. Via a self-medication framework, trauma-related drinking to cope (TRD), an unexplored construct to date, may help explain why these two disorders co-occur, thus serving as an essential target for treatment and prevention efforts. The present study aimed to create a novel measure of TRD and examine its psychometric properties, investigate its indirect influences on the association between PTSD and AUP, as well as explore its potential shared molecular genetic risk with PTSD in a genetically-informative study of college students. A sample of 1,896 students with a history of trauma and alcohol use provided genotypic data and completed an online assessment battery. First, the psychometric properties of TRD and how it relates to relevant constructs were examined using descriptive statistics and structural equation modeling. Findings demonstrated support for the external validation of TRD, both with regard to PTSD and alcohol consumption and related problems, and suggested that TRD is a more specific measure of drinking to cope motives compared to the commonly used Drinking Motives Questionnaire coping subscale. Second, results from a correlated multiple mediator model indicated that, while accounting for the effects of generalized drinking motives, TRD partially mediated the relation between PTSD and AUP and that this relationship was stronger for males than for females. Results were substantiated using longitudinal data. Third, univariate and bivariate genotypic analyses were conducted for TRD and PTSD, most of which resulted in null findings likely due to insufficient sample sizes. However, genome wide association analysis identified several significant genetic variants associated with TRD in participants of European Ancestry. Genes associated with TRD included PRAME, a protein coding gene with antithetical effects to genes commonly implicated in alcohol metabolism, as well as several genes implicated in immune system functioning (e.g., IGH, IGHE, ELK2AP). Polygenic risk for PTSD was associated with PTSD in the present sample and nominally associated with TRD. Findings are discussed in the context of limitations, clinical implications, and future directions

THE BUFFERING EFFECTS OF RESILIENCE ON ALCOHOL USE: A PHENOTYPIC AND GENOTYPIC INVESTIGATION

The college years encompass a time of vulnerability for problematic alcohol use/alcohol use disorder (AUD) and exposure to traumatic events (TE), which is a transdiagnostic risk factor for AUD, posttraumatic stress disorder (PTSD), and comorbid AUD-PTSD. However, not all who experience a TE develop these disorders, highlighting the need to identify factors that impact post-trauma outcomes. Resilience has been shown to be associated with lower alcohol consumption and related problems following TE, though the buffering effects of resilience on alcohol use have not yet been examined. Further, twin studies demonstrate that resilience is moderately heritable, but further research is needed to understand the molecular genetics of resilience (e.g., establishment of molecular heritability, identification of individual variants associated with resilience, examination of overall aggregate genetic risk in relation to AUD, PTSD, and other putative protective factors). Using data of the TE exposed subsample of a larger genetically informative longitudinal cohort study of college students (i.e., Spit for Science, N=7,367), the present study had three aims: 1) investigate the buffering effect of resilience against new onset TEs on alcohol use phenotypes; 2) identify individual variants associated with resilience, as well as examine the overall heritability of resilience and 3) examine the aggregate genetic overlap of resilience with alcohol use phenotypes, PTSD, and other protective factors using aggregate risk analyses. First, resilience was examined as a buffer against new onset TE on various alcohol use outcomes using a longitudinal path analysis framework. Findings demonstrated that resilience acts as a buffer in the wake of college onset TE against AUD symptoms, but not for alcohol consumption nor binge drinking status. Second, the genetic underpinnings of resilience were investigated by examining individual variants using genome wide association study (GWAS) analyses, and by calculating the SNP-based heritability via genome-wide complex trait analysis (GCTA). Meta-analyzed GWAS identified no SNPs meeting genome-wide significance, but revealed 9 SNPs meeting the suggestive of significance threshold that should be examined in future research with larger samples sizes. The majority of these SNPs mapped on to the SEZ6L gene, implicated in Bipolar Disorder and seizure activity, as well as a cluster of genes located on chromosome 8 associated with the metabolism of vitamins such as Vitamin B folate and Vitamin E, and as such, implicated in inflammatory response. GCTA estimated modest heritability for resilience, but the estimates did not differ significantly from zero. Lastly, polygenic risk scores (PRS) were used to examine the genetic correlation between resilience and alcohol dependence (AD), alcohol consumption, PTSD, and subjective well-being. Findings support polygenic risk for alcohol consumption as related to resilience in the EUR sub-sample only, and polygenic risk for PTSD as associated with resilience in the AFR sub-sample only. Findings are further discussed in the context of clinical implications, limitations, and future directions

Genome wide association study of uric acid in Indian population and interaction of identified variants with type 2 diabetes

Abnormal level of Serum Uric Acid (SUA) is an important marker and risk factor for complex diseases including Type 2 diabetes. Since genetic determinant of uric acid in Indians is totally unexplored, we tried to identify common variants associated with SUA in Indians using Genome Wide Association Study (GWAS). Association of five known variants in SLC2A9 and SLC22A11 genes with SUA level in 4,834 normoglycemics (1,109 in discovery and 3,725 in validation phase) was revealed with different effect size in Indians compared to other major ethnic population of the world. Combined analysis of 1,077 T2DM subjects (772 in discovery and 305 in validation phase) and normoglycemics revealed additional GWAS signal in ABCG2 gene. Differences in effect sizes of ABCG2 and SLC2A9 gene variants were observed between normoglycemics and T2DM patients. We identified two novel variants near long non-coding RNA genes AL356739.1 and AC064865.1 with nearly genome wide significance level. Meta-analysis and in silico replication in 11,745 individuals from AUSTWIN consortium improved association for rs12206002 in AL356739.1 gene to sub-genome wide association level. Our results extends association of SLC2A9, SLC22A11 and ABCG2 genes with SUA level in Indians and enrich the assemblages of evidence for SUA level and T2DM interrelationship

Drinking Motives Underlying Internalizing and Externalizing Pathways to Alcohol Misuse in College Students

Alcohol misuse, including heavy episodic use and negative consequences, is a major public health concern and a particular problem among college students. The etiology of alcohol misuse is not well resolved, with multiple and often contradictory factors implicated in its development. Genetic factors influence alcohol misuse but few specific genes have been identified. A potential reason for these challenges is that alcohol misuse is phenotypically and genetically heterogeneous; that is, there are multiple causal pathways underlying its development. Previous typologies have suggested that distinct internalizing and externalizing pathways are involved, with corresponding differences in profiles of personality, temperament, and comorbid psychopathology. Drinking motives, specifically drinking for positive reinforcement versus negative reinforcement motives, map intuitively onto such pathways and may provide a mechanism explaining their development. The aim of this project was to utilize drinking motives as intermediate phenotypic measures to investigate genetic and environmental factors contributing to the hypothesized diverging internalizing and externalizing pathways to alcohol misuse in a prospective, longitudinal sample of college students. Mixture modeling approaches identified distinct internalizing and externalizing subgroups with both quantitative and qualitative differences in traits/symptoms. The externalizing subgroup had a broader risk profile and elevated levels of both types of drinking motives, while the internalizing subgroup had specifically elevated levels of internalizing symptoms and negative reinforcement motives. Longitudinal analyses indicated stability of drinking motives throughout college and differential associations between positive/negative reinforcement motives and internalizing, externalizing, and alcohol misuse measures. Cross-lagged structural equation models pointed to a causal direction of effect of positive reinforcement motives on alcohol misuse. Finally, a series of genetic association analyses identified some promising genes and genetic variants underlying drinking motives and internalizing psychopathology, though their genetic etiologies remain largely inconclusive. The results of this project tie together several parallel lines of research on alcohol misuse and in the broader psychiatric genetics field. Findings support the existence of distinct, though not wholly separate, internalizing and externalizing subgroups, and suggest that the intermediate mechanisms of drinking motives are a valuable tool through which to understand these heterogeneous pathways to alcohol misuse

Sleep disturbances and depression: the role of genes and trauma

Sleep disturbances and insomnia are prevalent, with around 33% of adults indicating that they experience at least one main symptom of insomnia, and bidirectional relationships exist with common psychopathology, particularly major depressive disorder (MDD). However, genetic and environmental (e.g., traumatic event exposure) contributions to the etiology of these phenotypes are not yet well understood. A genetically informative sample of approximately 12,000 Han Chinese women aged 30-60 (50% with recurrent MDD) was used to address several gaps within the sleep literature. Sleep disturbances were assessed in all individuals using a general item addressing sleeplessness (GS). A sleep within depression sum score (SDS) was also created in MDD cases, combining information from the GS and two insomnia items within MDD. A total of 11 traumatic events were assessed and additional information on childhood sexual abuse (CSA) was also obtained. First, factor analyses were conducted to determine trauma factor structure. The best-fit solution included 3 factors: interpersonal, child interpersonal, and non-assaultive, and composite variables were constructed accordingly. A series of hierarchical regressions were run to examine differential effects of trauma type and timing on sleeplessness. All traumatic events predicted sleeplessness at similar magnitudes, although population models indicated that childhood interpersonal trauma may be particularly potent. An association between CSA and sleeplessness was also replicated. A series of genetic analyses demonstrated that the single nucleotide polymorphism-based heritability of sleep phenotypes did not differ significantly from zero. Further, association analyses did not identify any genome-wide significant loci. However, using a liberal false discovery rate threshold of 0.5, two genes of interest, KCNK9 and ALDH1A2, emerged for the SDS. Polygenic risk score (PRS) analyses demonstrated genetic overlap between the SDS in MDD cases and GS in MDD controls, with PRSs explaining 0.2-0.3% of the variance. A final combined model of both genetic and environmental risk indicated that both PRS and traumatic events were significant predictors of sleeplessness. While genetic results should be interpreted with caution given the lack of heritability, additional research into the genetic and environmental contributions to insomnia, utilizing more standardized phenotypes and properly ascertained samples, is clearly warranted

Statistical Methods for Genetic Prediction of Complex Traits in Single and Multiple Populations

Genetic prediction of complex traits, also known as polygenic risk score (PRS), is constructed by combining the estimated effect sizes of genetic markers across the genome for an individual. PRS has shown great promise in biomedical and clinical research for disease prevention, monitoring and treatment. However, the development of accurate prediction models is challenging due to the wide diversity of genetic architecture, limited access to individual level data, and the demand for computational resources. The broader application of PRS to the general population is further hindered by the poor transferability of PRS developed in Europeans to non-European populations. In this thesis, we develop two statistical methods to help address these limitations. Chapter 1 includes a review of PRS from a statistical perspective. In Chapter 2, we present a summary statistics-based nonparametric method SDPR that is adaptive to different genetic architectures, statistically robust, and computationally efficient. The material is drawn from the manuscript “A fast and robust Bayesian nonparametric method for prediction of complex traits using summary statistics” with minor modification. In Chapter 3, we develop a statistical method called SDPRX that can effectively integrate genome wide association study summary statistics from different populations to improve the prediction accuracy in non-European populations. The material is drawn from the manuscript “SDPRX: A statistical method for cross-population prediction of complex traits” in preparation

The breadbasket of Cape Town: Exploring the links between urban agriculture, land use and food security in the Philippi Horticultural Area (PHA)

Magister Artium - MAHunger is more than just a feeling, it is the lack of access to safe nutritious food, which in turn may result in anger towards government, low performance, sadness and a limited will to survive. Urban agriculture has been identified as a source of livelihood for many urban residents and could fundamentally change food insecure cities like Cape Town. The Philippi Horticultural Area (PHA) is one such place with an enormous amount of potential to assist the City of Cape Town (CCT) to overcome food insecurity challenges. The PHA is the focus of this thesis that aims to determine the impacts that housing and industrial developments in the PHA have had, and might have in the future, on food security in the Greater Cape Town Area (GCTA). The specific objectives of the study are as follows: (1) To investigate the urban agricultural distribution of the PHA; (2) to investigate agricultural facilitation, people empowerment and the use of land for agricultural purposes; (3) To determine the level of access to food for people within and around the PHA; and (4) To examine the links between the urban agricultural food sector and food production