Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Publisher Copyright: © 2022, The Author(s).Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.Peer reviewe

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P = 9.89 × 10− 6), and rs7700147, an intergenic variant (P = 2.93 × 10− 5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6), and rs7700147, an intergenic variant (P=2.93 × 10 -5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes

Microstructural characteristics of naturally formed hardpan capping sulfidic copper-lead-zinc tailings

A massive and dense textured layer (ca. 35–50 cm thick) of hardpan was uncovered at the top layer, which capped the unweathered sulfidic Cu-Pb-Zn tailings in depth and physically supported gravelly soil root zones sustaining native vegetation for more than a decade. For the purpose of understanding functional roles of the hardpan layer in the cover profile, the present study has characterized the microstructures of the hardpan profile at different depth compared with the tailings underneath the hardpans. A suit of microspectroscopic technologies was deployed to examine the hardpan samples, including field emission-scanning electron microscopy coupled with energy dispersive spectroscopy (FE-SEM-EDS), X-ray diffraction (XRD) and synchrotron-based X-ray absorption fine structure spectroscopy (XAFS). The XRD and Fe K-edge XAFS analysis revealed that pyrite in the tailings had been largely oxidised, while goethite and ferrihydrite had extensively accumulated in the hardpan. The percentage of Fe-phyllosilicates (e.g., biotite and illite) decreased within the hardpan profile compared to the unweathered tailings beneath the hardpan. The FE-SEM-EDS analysis showed that the fine-grained Ca-sulfate (possibly gypsum) evaporites appeared as platelet-shaped that deposited around pyrite, dolomite, and crystalline gypsum particles, while Fe-Si gels exhibited a needle-like texture that aggregated minerals together and produced contiguous coating on pyrite surfaces. These microstructural findings suggest that the weathering of pyrite and Fe-phyllosilicates coupled with dolomite dissolution may have contributed to the formation of Ca-sulfate/gypsum evaporites and Fe-Si gels. These findings have among the first to uncover the microstructure of hardpan formed at the top layer of sulfidic Cu-Pb-Zn tailings, which physically capped the unweathered tailings in depth and supported root zones and native vegetation under semi-arid climatic conditions

Rhizosphere modifications of iron-rich minerals and forms of heavy metals encapsulated in sulfidic tailings hardpan

Hardpan caps formed after extensive weathering of the top layer of sulfidic tailings have been advocated to serve as physical barriers separating reactive tailings in depth and root zones above. However, in a hardpan-based root zone reconstructed with the soil cover, roots growing into contact with hardpan surfaces may induce the transformation of Fe-rich minerals and release potentially toxic elements for plant uptake. For evaluating this potential risk, two representative native species, Turpentine bush (Acacia chisholmii, AC) and Red Flinders grass (Iseilema vaginiflorum, RF), of which pre-cultured root mats were interfaced with thin discs of crushed hardpan minerals in the rhizosphere (RHIZO) test. After 35 days, the surface dissolution of hardpan minerals occurred and Fe-rich cement minerals were transformed from ferrihydrite-like minerals to goethite-like and Fe(III)-carboxylic complexes, as revealed by scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and synchrotron-based X-ray absorption fine structure spectroscopy (XAFS) analysis. This transformation may result from the functions of root exudates. The transformation of hardpan cement minerals caused the co-dissolution of Cu and Zn initially encapsulated in the cements and their uptake by plants. Nevertheless, only was the minority of the plant Cu and Zn transported into shoots

Ecological engineering of iron ore tailings into useable soils for sustainable rehabilitation

Summary: Ecological engineering of soil formation in tailings is an emerging technology toward sustainable rehabilitation of iron (Fe) ore tailings landscapes worldwide, which requires the formation of well-organized and stable soil aggregates in finely textured tailings. Here, we demonstrate an approach using microbial and rhizosphere processes to progressively drive aggregate formation and development in Fe ore tailings. The aggregates were initially formed through the agglomeration of mineral particles by organic cements derived from microbial decomposition of exogenous organic matter. The aggregate stability was consolidated by colloidal nanosized Fe(III)-Si minerals formed during Fe-bearing primary mineral weathering driven by rhizosphere biogeochemical processes of pioneer plants. From these findings, we proposed a conceptual model for progressive aggregate structure development in the tailings with Fe(III)-Si rich cements as core nuclei. This renewable resource dependent eco-engineering approach opens a sustainable pathway to achieve resilient tailings rehabilitation without resorting to excavating natural soil resources