Women Talking about Water: Feminist Subjectivities and Intersectional Understandings

In this study based on discussions held by women\u27s groups across Canada on water challenges and interests, we recognized that in the current context in Canada, women are truly connected with peoples, humans or any other form of life. They recognize that water is socially embedded, integrating issues of social, ecological and intergenerational justice in relation to complex changes in riparian landscapes. Clearly their talk is from a gender perspective, but we also found movement beyond gender that nuanced cross-sectoral understanding, critical links between gender, class and ethnicity are frequently mentioned

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleve

Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain

Association of Low-Frequency and Rare Coding-Sequence Variants with Blood Lipids and Coronary Heart Disease in 56,000 Whites and Blacks

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the “Exome Array” to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121∗], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Navigating water access and governance in peri-urban Ashaiman, Ghana : a case study

Low-income, peri-urban residents of Greater Accra face disparities in water access, particularly given that piped water services provided by the formal municipal network are highly erratic and unreliable. Often, those underserved by the official provider are able to meet their daily water needs by sourcing water through alternative, or informal, means. Although it is often the case that informal water services pose important challenges for users, for instance in terms of price and quality, this research attempts to understand other dimensions of how populations are served when they are not adequately reached by formal networks. This research also explores the potential for participatory water governance, querying policy and scholarly literatures that advocate for a more inclusive water governance process on the grounds that it is key towards service extension and empowerment. This thesis is based on two months of fieldwork in Ashaiman, a rapidly growing settlement located on the outskirts of the capital region of Accra, Ghana. The overall objective of the thesis is twofold: (1) To examine the myriad of mediums and networks through which water is accessed, with particular attention to those that extend beyond the municipal water system, and (2) To assess how participation in water governance is experienced and expressed by the peri-urban poor, with the aim of considering possibilities for managing water concerns in this context. These themes are addressed respectively in the two substantive chapters of this thesis. Insights suggest that a diversity of strategies to obtain water is a key factor in allowing peri-urban dwellers to cope with water insecurities. In addition, mainstream approaches to participatory water governance may be at odds with local institutions operating within Ashaiman, which tend to be multi-purpose and adaptive, based on a wide-ranging goal of improving social welfare. Among other implications of these findings, it is concluded that an in-depth process of consultation with community members, organizations and private water vendors is imperative to promote collaborative governance of water and well-being, where members themselves define the scope of the mandate, and where the critical role of informal water networks is accounted for.Science, Faculty ofResources, Environment and Sustainability (IRES), Institute forGraduat

'Chasing for Water': Everyday Practices of Water Access in Peri-Urban Ashaiman, Ghana

Despite recent reports suggesting that access to improved sources of drinking water is rising in Ghana, water access remains a daily concern for many of those living in the capital region. Throughout the Greater Accra Metropolitan Area (GAMA), the urban poor manage uncertainty and establish themselves in the city by leveraging a patchwork system of basic services that draws importantly from informal systems and supplies. This paper takes a case study approach, using evidence gathered from two-months of fieldwork in a peri-urban informal settlement on the fringe of Accra, to explore everyday practices involved in procuring water for daily needs that routinely lead residents outside of the official water supply system. Findings from this case study demonstrate that respondents make use of informal water services to supplement or 'patch up' gaps left by the sporadic water flow of the official service provider, currently Ghana Water Company Ltd. (GWCL). Basic water access is thus constructed through an assemblage of coping strategies and infrastructures. This analysis contributes to understandings of heterogeneity in water access by attending to the everyday practices by which informality is operationalised to meet the needs of the urban poor, in ways that may have previously been overshadowed. This research suggests, for example, that although water priced outside of the official service provider is generally higher per unit, greater security may be obtained from smaller repetitive transactions as well as having the flexibility to pursue multiple sources of water on a day-to-day basis