SwePub - search: WFRF:(Wilson Katherine M)

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1.	Roth, GA, et al. (author) Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 In: Lancet (London, England). - 1474-547X .- 0140-6736. ; 392:10159, s. 1736-1788 Journal article (peer-reviewed)
2.	Abbafati, Cristiana, et al. (author) 2020 Journal article (peer-reviewed)
3.	Kanoni, Stavroula, et al. (author) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Journal article (peer-reviewed)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
4.	Loza, M. J., et al. (author) Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study 2016 In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1 Journal article (peer-reviewed)abstract Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
5.	Marouli, Eirini, et al. (author) Rare and low-frequency coding variants alter human adult height 2017 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190 Journal article (peer-reviewed)abstract Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and 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.
6.	Sampson, Joshua N., et al. (author) Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types 2015 In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12 Journal article (peer-reviewed)abstract Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
7.	Turcot, Valerie, et al. (author) Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity 2018 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
8.	Hollestelle, Antoinette, et al. (author) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer 2016 In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401 Journal article (peer-reviewed)abstract Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
9.	Justice, Anne E., et al. (author) Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution 2019 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469 Journal article (peer-reviewed)abstract Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
10.	Palmer, Nicholette D, et al. (author) A genome-wide association search for type 2 diabetes genes in African Americans. 2012 In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202- Journal article (peer-reviewed)abstract African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
11.	Craddock, Nick, et al. (author) Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls 2010 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720 Journal article (peer-reviewed)abstract Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
12.	The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data 2022 In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2 Journal article (peer-reviewed)abstract This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
13.	Weinstein, John N., et al. (author) The cancer genome atlas pan-cancer analysis project 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120 Research review (peer-reviewed)abstract The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
14.	Sodergren, Erica, et al. (author) The genome of the sea urchin Strongylocentrotus purpuratus. 2006 In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52 Journal article (peer-reviewed)abstract We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
15.	Lunetta, Kathryn L., et al. (author) Rare coding variants and X-linked loci associated with age at menarche 2015 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6 Journal article (peer-reviewed)abstract More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
16.	Voight, Benjamin F., et al. (author) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis 2010 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589 Journal article (peer-reviewed)abstract By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
17.	Lewin, Harris A., et al. (author) The Earth BioGenome Project 2020 : Starting the clock 2022 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4 Journal article (other academic/artistic)
18.	Sakornsakolpat, Phuwanat, et al. (author) Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations 2019 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505 Journal article (peer-reviewed)abstract Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
19.	Schweinsberg, Martin, et al. (author) Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis 2021 In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249 Journal article (peer-reviewed)abstract In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
20.	Shrine, Nick, et al. (author) New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries 2019 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493 Journal article (peer-reviewed)abstract Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
21.	Moshontz, Hannah, et al. (author) The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network 2018 In: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515 Journal article (peer-reviewed)abstract Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
22.	Patterson, Nick, et al. (author) Large-scale migration into Britain during the Middle to Late Bronze Age 2022 In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594 Journal article (peer-reviewed)abstract Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
23.	Simone, Roberto, et al. (author) G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology invitro and invivo. 2018 In: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 10:1, s. 22-31 Journal article (peer-reviewed)abstract Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G-quadruplex RNA We investigated their effect in C9orf72 patient iPSC-derived motor and cortical neurons and show that they significantly reduce RNA foci burden and the levels of dipeptide repeat proteins. Furthermore, they also reduce dipeptide repeat proteins and improve survival invivo, in GGGGCC repeat-expressing Drosophila Therefore, small molecules that target GGGGCC repeat G-quadruplexes can ameliorate the two key pathologies associated with C9orf72 FTD/ALS These data provide proof of principle thattargeting GGGGCC repeat G-quadruplexes has therapeutic potential.
24.	Wilson, Katherine M, et al. (author) Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. 2022 In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 93:7, s. 761-771 Journal article (peer-reviewed)abstract A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay.We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS.We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.
25.	Clayton, Emma L., et al. (author) Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation 2017 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:5, s. 873-887 Journal article (peer-reviewed)abstract Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.
26.	Gloster, Tracey M., et al. (author) Characterization and three-dimensional structures of two distinct bacterial xyloglucanases from families GH5 and GH12 2007 In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:26, s. 19177-19189 Journal article (peer-reviewed)abstract The plant cell wall is a complex material in which the cellulose microfibrils are embedded within a mesh of other polysaccharides, some of which are loosely termed hemicellulose. One such hemicellulose is xyloglucan, which displays a beta-1,4-linked D-glucose backbone substituted with xylose, galactose, and occasionally fucose moieties. Both xyloglucan and the enzymes responsible for its modification and degradation are finding increasing prominence, reflecting both the drive for enzymatic biomass conversion, their role in detergent applications, and the utility of modified xyloglucans for cellulose fiber modification. Here we present the enzymatic characterization and three-dimensional structures in ligand free and xyloglucan- oligosaccharide complexed forms of two distinct xyloglucanases from glycoside hydrolase families GH5 and GH12. The enzymes, Paenibacillus pabuli XG5 and Bacillus licheniformis XG12, both display open active center grooves grafted upon their respective (beta/alpha)(8) and beta-jelly roll folds, in which the side chain decorations of xyloglucan may be accommodated. For the beta-jelly roll enzyme topology of GH12, binding of xylosyl and pendant galactosyl moieties is tolerated, but the enzymeis similarly competent in the degradation of unbranched glucans. In the case of the (beta/alpha)(8) GH5 enzyme, kinetically productive interactions are made with both xylose and galactose substituents, as reflected in both a high specific activity on xyloglucan and the kinetics of a series of aryl glycosides. The differential strategies for the accommodation of the side chains of xyloglucan presumably facilitate the action of these microbial hydrolases in milieus where diverse and differently substituted substrates may be encountered.
27.	Lindblad-Toh, Kerstin, et al. (author) A high-resolution map of human evolutionary constraint using 29 mammals 2011 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482 Journal article (peer-reviewed)abstract The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
28.	Cohen, Joachim, et al. (author) Differences in place of death between lung cancer and COPD patients : a 14-country study using death certificate data 2017 In: npj Primary Care Respiratory Medicine. - : Springer Science and Business Media LLC. - 2055-1010. ; 27 Journal article (peer-reviewed)abstract Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life. Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before. We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information. We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death. Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease. Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France. In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea. Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries. Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home. This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.
29.	Concepcion Gil-Rodriguez, Maria, et al. (author) De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes 2015 In: Human Mutation. - : Wiley: 12 months. - 1059-7794 .- 1098-1004. ; 36:4, s. 454-462 Journal article (peer-reviewed)abstract Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for approximate to 1%-2% of CdLS-like phenotypes.
30.	Harding, Richard, et al. (author) Place of death for people with HIV : a population-level comparison of eleven countries across three continents using death certificate data 2018 In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 18:1 Journal article (peer-reviewed)abstract BACKGROUND: With over 1 million HIV-related deaths annually, quality end-of-life care remains a priority. Given strong public preference for home death, place of death is an important consideration for quality care. This 11 country study aimed to i) describe the number, proportion of all deaths, and demographics of HIV-related deaths; ii) identify place of death; iii) compare place of death to cancer patients iv), determine patient/health system factors associated with place of HIV-related death.METHODS: In this retrospective analysis of death certification, data were extracted for the full population (ICD-10 codes B20-B24) for 1-year period: deceased's demographic characteristics, place of death, healthcare supply.RESULTS: i) 19,739 deaths were attributed to HIV. The highest proportion (per 1000 deaths) was for Mexico (9.8‰), and the lowest Sweden (0.2‰). The majority of deaths were among men (75%), and those aged <50 (69.1%). ii) Hospital was most common place of death in all countries: from 56.6% in the Netherlands to 90.9% in South Korea. The least common places were hospice facility (3.3%-5.7%), nursing home (0%-17.6%) and home (5.9%-26.3%).iii) Age-standardised relative risks found those with HIV less likely to die at home and more likely to die in hospital compared with cancer patients, and in most countries more likely to die in a nursing home. iv) Multivariate analysis found that men were more likely to die at home in UK, Canada, USA and Mexico; a greater number of hospital beds reduced the likelihood of dying at home in Italy and Mexico; a higher number of GPs was associated with home death in Italy and Mexico.CONCLUSIONS: With increasing comorbidity among people ageing with HIV, it is essential that end-of-life preferences are established and met. Differences in place of death according to country and diagnosis demonstrate the importance of ensuring a "good death" for people with HIV, alongside efforts to optimise treatment.
31.	Karriker-Jaffe, Katherine J., et al. (author) Can alcohol policy prevent harms to women and children from men's alcohol consumption? An overview of existing literature and suggested ways forward 2023 In: International journal of drug policy. - 0955-3959 .- 1873-4758. ; 119 Journal article (peer-reviewed)abstract The World Health Organization's list of cost-effective alcohol control policies is a widely-used resource that highlights strategies to address alcohol-related harms. However, there is more evidence on how recommended policies impact harms to people who drink alcohol-such as physical health problems caused by heavy alcohol use-than on secondhand harms inflicted on someone other than the person drinking alcohol, i.e., alcohol's harms to others. In this essay, we describe evidence of impacts of alcohol policy on harms to women and children resulting from men's alcohol consumption, as well as options for making policies more relevant for reducing intimate partner violence and child abuse. We begin with an overview of harms to women and children resulting from men's alcohol consumption and review cost-effective alcohol policies with potential to reduce these harms based on likely mechanisms of action. Next, we present a rapid review of reviews to describe existing evidence of impacts of these policies on the outcomes of physical violence, sexual violence, and child abuse and neglect. We found little evidence of systematic evaluation of impacts of these important alcohol policies on harms to women and children. Thus, we advocate for increased attention in evaluation research to the impacts of alcohol policies on harms experienced by women and children who are exposed to men who drink alcohol. We also argue for more consideration of a broader range of policies and interventions to reduce these specific types of harm. Finally, we present a conceptual model illustrating how alcohol policies may be supplemented with other interventions specifically tailored to reduce alcohol-related harms commonly experienced by women and children as a result of men's alcohol use.
32.	Laslett, Anne-Marie, et al. (author) Children's experience of physical harms and exposure to family violence from others' drinking in nine societies 2020 In: Addiction Research and Theory. - : Informa UK Limited. - 1606-6359 .- 1476-7392. ; 28:4, s. 354-364 Journal article (peer-reviewed)abstract Aim: To study caregiver reports of children's experience of physical harm and exposure to family violence due to others' drinking in nine societies, assess the relationship of harm with household drinking pattern and evaluate whether gender and education of caregiver affect these relationships. Method: Using data on adult caregivers from the Gender and Alcohol's Harm to Others (GENAHTO) project, child alcohol-related injuries and exposure of children to alcohol-related violence (CAIV) rates are estimated by country and pooled using meta-analysis and stratified by gender of the caregiver. Households with and without heavy or harmful drinker(s) (HHDs) are compared to assess the interaction of caregiver gender on the relationship between reporting HHD and CAIV, adjusting for caregiver education and age. Additionally, the relationship between caregiver education and CAIV is analyzed with meta-regression. Results: The prevalence of CAIV varied across societies, with an overall pooled mean of 4% reported by caregivers. HHD was a consistent correlate of CAIV in all countries. Men and women in the sample reported similar levels of CAIV overall, but the relationship between HHD and CAIV was greater for women than for men, especially if the HHD was the most harmful drinker (MHD). Education was not significantly associated with CAIV. Conclusions: One in 25 caregivers with children report physical or family violence harms to children because of others' drinking. The adjusted odds of harm are significantly greater (more than four-fold) in households with an HHD, with men most likely to be defined as this drinker in the household.
33.	Lee, K S Kylie, et al. (author) Developing a tablet computer-based application ('App') to measure self-reported alcohol consumption in Indigenous Australians 2018 In: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947. ; 18:1 Journal article (peer-reviewed)abstract BACKGROUND: The challenges of assessing alcohol consumption can be greater in Indigenous communities where there may be culturally distinct approaches to communication, sharing of drinking containers and episodic patterns of drinking. This paper discusses the processes used to develop a tablet computer-based application ('App') to collect a detailed assessment of drinking patterns in Indigenous Australians. The key features of the resulting App are described.METHODS: An iterative consultation process was used (instead of one-off focus groups), with Indigenous cultural experts and clinical experts. Regular (weekly or more) advice was sought over a 12-month period from Indigenous community leaders and from a range of Indigenous and non-Indigenous health professionals and researchers.RESULTS: The underpinning principles, selected survey items, and key technical features of the App are described. Features include culturally appropriate questioning style and gender-specific voice and images; community-recognised events used as reference points to 'anchor' time periods; 'translation' to colloquial English and (for audio) to traditional language; interactive visual approaches to estimate quantity of drinking; images of specific brands of alcohol, rather than abstract description of alcohol type (e.g. 'spirits'); images of make-shift drinking containers; option to estimate consumption based on the individual's share of what the group drank.CONCLUSIONS: With any survey platform, helping participants to accurately reflect on and report their drinking presents a challenge. The availability of interactive, tablet-based technologies enables potential bridging of differences in culture and lifestyle and enhanced reporting.
34.	Testor, Pierre, et al. (author) OceanGliders: A component of the integrated GOOS 2019 In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6 Research review (peer-reviewed)abstract The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
35.	Weatherall, Teagan J., et al. (author) Alcohol dependence in a community sample of Aboriginal and Torres Strait Islander Australians : harms, getting help and awareness of local treatments 2021 In: Addiction science & clinical practice. - : Springer Science and Business Media LLC. - 1940-0632 .- 1940-0640. ; 16:1 Journal article (peer-reviewed)abstract Background: Few studies have examined links between current alcohol dependence and specific harms among Indigenous Australians. We investigated these associations as well as help seeking for drinking, awareness of local treatments and recommendations to help family or friends cut down or stop drinking in two Indigenous communities.Methods: A representative sample of Indigenous Australians was surveyed in one urban and one remote community in South Australia. Data were collected via the Grog Survey App. Participants were dependent if they reported two or more symptoms of alcohol dependence (ICD-11). Pearson chi-square tests were used to describe relationships between employment by gender, and dependence by awareness of medicines and local treatment options. Multivariate logistic regressions were used to predict the odds of dependent drinkers experiencing harms and getting help for drinking, controlling for age, gender, schooling and income.Results: A total of 775 Indigenous Australians took part in the study. After controlling for confounders, dependent drinkers were nearly eight times more likely to report a harm and nearly three times more likely to get help for their drinking—compared with non-dependent drinkers. Participants recommended accessing local support from an Aboriginal alcohol and other drugs worker, or a detoxification/ rehabilitation service.Discussion and conclusions: More support and funding is needed for Indigenous Australians to ensure local treatment options for dependent drinkers are readily available, appropriate and accessible. Involvement of local Aboriginal or Torres Strait Islander health professionals in delivery of care can help ensure that it is appropriate to an individual’s culture and context.
36.	Weatherall, Teagan J., et al. (author) Prevalence and correlates of alcohol dependence in an Australian Aboriginal and Torres Strait Islander representative sample : Using the Grog Survey App 2022 In: Drug and Alcohol Review. - : Wiley. - 0959-5236 .- 1465-3362. ; 41:1, s. 125-134 Journal article (peer-reviewed)abstract Introduction. Little is known about the prevalence of current alcohol dependence in Indigenous Australian communities. Here we identify the frequency of reported symptoms, estimate the prevalence and describe the correlates of current alcohol dependence. Methods. A representative sample of Indigenous Australians (16+ years) was recruited from an urban and remote community in South Australia. Data were collected between July and October 2019 via a tablet computer-based application. Participants were likely dependent if they reported two or more dependence symptoms (ICD-11; in the last 12 -months), weekly or more frequently. Chi-square tests described the relationship between demographics, remoteness and alcohol dependence. Spearman correlations estimated the relationship between symptoms of dependence, consumption characteristics and demographics. Results. A total of 775 Indigenous Australians participated. The most frequently reported symptoms were prioritising alcohol over other things and loss of control. Overall, 2.2% were likely dependent on alcohol (n = 17/775). Prevalence did not vary by remoteness. Participants who drank more and more frequently tended to report more frequent symptoms of dependence. In the urban site, men tended to report more frequent symptoms of dependence than women. Age, income and schooling were not linked to dependence. Discussion and Conclusions. The prevalence of current alcohol dependence in this representative sample was similar to that of the general Australian and international estimates. Understanding risk factors for current alcohol dependence will be useful to inform the allocation of funding and support. Accurate estimates of the prevalence of current alcohol dependence are important to better identify specialist treatment needs.

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