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2. A genome catalog of the early-life human skin microbiome

Author

Shen, Zeyang, Robert, Lukian, Stolpman, Milan, Che, You, Allen, Katrina J., Saffery, Richard, Walsh, Audrey, Young, Angela, Eckert, Jana, Deming, Clay, Chen, Qiong, Conlan, Sean, Laky, Karen, Li, Jenny Min, Chatman, Lindsay, Kashaf, Sara Saheb, Kong, Heidi H., Frischmeyer-Guerrerio, Pamela A., Perrett, Kirsten P., and Segre, Julia A.

Published
2023
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5. Bivariate mixture models for the joint distribution of repeated serum ferritin and transferrin saturation measured 12 years apart in a cohort of healthy middle-aged Australians.

Author

McLaren, Christine E, Chen, Wen-Pin, Bertalli, Nadine A, Delatycki, Martin B, Giles, Graham G, English, Dallas R, Hopper, John L, Allen, Katrina J, and Gurrin, Lyle C

Subjects
Adult, Amino Acid Substitution, Australia, Female, Ferritins, Hemochromatosis, Hemochromatosis Protein, Homozygote, Humans, Male, Middle Aged, Models, Biological, Mutation, Missense, Transferrin, Digestive Diseases, Prevention, Hematology, Genetics, Models, Biological, Mutation, Missense, MD Multidisciplinary, General Science & Technology
Abstract

Homozygosity for the p.C282Y substitution in the HFE protein encoded by the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. McLaren et al. used bivariate mixture modeling to analyze the joint population distribution of transferrin saturation (TS) and serum ferritin concentration (SF) measured for participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. They identified four components (C1, C2, C3, and C4) with successively increasing means for TS and SF. They demonstrated that bivariate mixture modeling in TS and SF reflect the genetic locus of HFE and may isolate p.C282Y homozygotes from the general population. In the current study we used data from the another large cohort, the Australian HealthIron study of genetic and environmental modifiers of hereditary hemochromatosis, to validate the component analysis approach, to examine stability of component proportions over time and to determine if TS and SF values from an individual move between components at baseline and follow-up. Because sampling fractions from each p.C282Y / p.H63D genotype stratum are not equal, we used frequency weights based on the inverse of the probability of selection for invitation to participate. In the weighted female analytic cohorts, C4 captured most of C282Y homozygotes, and C2 was the largest component. We identified four components from the weighted male analytic cohort and C4 captured most of p.C282Y homozygotes. The bivariate mixture modeling approach suggested that the model is transferable from one white population to another, although estimated means within components may differ.

Published
2019

6. Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

Author

Messina, Nicole L., Gardiner, Kaya, Pittet, Laure F., Forbes, Emily K., Francis, Kate L., Freyne, Bridget, Zufferey, Christel, Abruzzo, Veronica, Morison, Clare, Turner, Hannah, Allen, Katrina J., Flanagan, Katie L., Ponsonby, Anne‐Louise, Robins‐Browne, Roy, Shann, Frank, Vuillermin, Peter, Donath, Susan, Casalaz, Dan, and Curtis, Nigel

Subjects
DELIVERY (Obstetrics), HEPATITIS B vaccines, FOOD allergy, BCG vaccines, RANDOMIZED controlled trials
Abstract

Background: The beneficial off‐target effects of Bacille Calmette–Guérin (BCG) vaccination potentially include protection against allergy. Objective: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. Methods: In this randomised controlled trial, 1272 neonates were allocated to BCG‐Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3‐monthly online questionnaires and oral food challenges. Data were analysed by intention‐to‐treat using binary regression. Clinicaltrials.gov (NCT01906853). Results: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI −1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI −3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). Conclusions and Clinical Relevance: Neonatal BCG‐Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Population Screening for Hereditary Haemochromatosis—Should It Be Carried Out, and If So, How?

Author

Delatycki, Martin B. and Allen, Katrina J.

Subjects
*IRON overload, *GENETIC testing, *IRON in the body, *MEDICAL economics, *HUMAN genome
Abstract

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted to be polygenic or at least gene-environment modified. Hereditary haemochromatosis (HH) is an inherited iron overload disorder, for which the vast majority of affected individuals (>90%) have homozygosity for a single pathogenic variant in the HFE gene, resulting in p.Cys282Tyr. Further, there is significant benefit to an individual in identifying the genetic risk of HH, since the condition evolves over decades, and the opportunity to intervene and prevent disease is both simple and highly effective through regular venesection. Add to that the immediate benefit to society of an increased pool of ready blood donors (blood obtained from HH venesections can generally be used for donation), and the case for population screening to identify those genetically at risk for HH becomes more cogent. Concerns about genetic discrimination, creating a cohort of "worried well", antipathy to acting on medical advice to undertake preventive venesection or simply not understanding the genetic risk of the condition adequately have all been allayed by a number of investigations. So why then has HH population genetic screening not been routinely implemented anywhere in the world? The answer is complex, but in this article we explore the pros and cons of screening for HH and the different views regarding whether it should be phenotypic (screening for iron overload by serum ferritin and/or transferrin saturation) or genotypic (testing for HFE p.Cys282Tyr). We argue that now is the time to give this poster child for population genetic screening the due consideration required to benefit the millions of individuals at risk of HFE-related iron overload. [ABSTRACT FROM AUTHOR]

Published
2024
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9. HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype‐stratified cohort study of hemochromatosis in Australian women

Author

Warne, Charles D, Zaloumis, Sophie G, Bertalli, Nadine A, Delatycki, Martin B, Nicoll, Amanda J, McLaren, Christine E, Hopper, John L, Giles, Graham G, Anderson, Greg J, Olynyk, John K, Powell, Lawrie W, Allen, Katrina J, Gurrin, Lyle C, and Investigators, for the HealthIron Study

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Liver Disease, Genetics, Aging, Contraception/Reproduction, Hematology, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Australia, Cohort Studies, Female, Ferritins, Genetic Predisposition to Disease, Genotype, Hemochromatosis, Hemochromatosis Protein, Homozygote, Humans, Menopause, Middle Aged, Mutation, hereditary hemochromatosis, HFE p, C282Y homozygosity, iron accumulation, iron overload-related disease, menopause, women's health, HealthIron Study Investigators, HFE p.C282Y homozygosity, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background and aimWomen who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably because of the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild types) as comparison groups.MethodsA sample of the Melbourne Collaborative Cohort Study was selected for the "HealthIron" study (n = 1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing.ResultsFor p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P

Published
2017

10. GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes

Author

Barton, James C, Chen, Wen-pin, Emond, Mary J, Phatak, Pradyumna D, Subramaniam, V Nathan, Adams, Paul C, Gurrin, Lyle C, Anderson, Gregory J, Ramm, Grant A, Powell, Lawrie W, Allen, Katrina J, Phillips, John D, Parker, Charles J, McLaren, Gordon D, and McLaren, Christine E

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Substance Misuse, Clinical Research, Alcoholism, Alcohol Use and Health, Cardiovascular, Good Health and Well Being, Acyltransferases, Adult, Age Factors, Aged, Alcohol Drinking, Female, Hemochromatosis Protein, Homozygote, Humans, Iron, Male, Middle Aged, Mutation, Missense, Hemochromatosis Iron overload, rs11558492, rs1800562, Hemochromatosis, Iron overload, Clinical Sciences, Immunology, Cardiovascular medicine and haematology
Abstract

BackgroundGNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes.MethodsWe defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin

Published
2017

14. Skin Prick Test Predictive Values for the Outcome of Cashew Challenges in Children

Author

Dwyer, Terence, Lowe, Adrian, Wake, Melissa, Robertson, Colin, Sawyer, Susan, Patton, George, Douglass, Jo, Vuillermin, Peter, McWilliam, Vicki, Peters, Rachel L., Allen, Katrina J., Dharmage, Shyamali C., Ponsonby, Anne-Louise, Tang, Mimi L.K., Smart, Joanne, Perrett, Kirsten, Tey, Dean, Robinson, Marnie, Taranto, Mark, Koplin, Jennifer J., and Gurrin, Lyle C.

Published
2020
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17. Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens

Author

Westerhout, Joost, Baumert, Joseph L., Blom, W. Marty, Allen, Katrina J., Ballmer-Weber, Barbara, Crevel, René W.R., Dubois, Anthony E.J., Fernández-Rivas, Montserrat, Greenhawt, Matthew J., Hourihane, Jonathan O'B., Koplin, Jennifer J., Kruizinga, Astrid G., Le, Thuy-My, Sampson, Hugh A., Shreffler, Wayne G., Turner, Paul J., Taylor, Steve L., Houben, Geert F., and Remington, Benjamin C.

Published
2019
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19. HFE C282Y and H63D simple heterozygosity

Author

Zaloumis, Sophie G, Allen, Katrina J, Bertalli, Nadine A, Turkovic, Lidija, Delatycki, Martin B, Nicoll, Amanda J, McLaren, Christine E, English, Dallas R, Hopper, John L, Giles, Graham G, Anderson, Gregory J, Olynyk, John K, Powell, Lawrie W, Gurrin, Lyle C, and Investigators, HealthIron Study

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Liver Disease, Digestive Diseases, Genetics, Hematology, Clinical Research, Chronic Liver Disease and Cirrhosis, Adult, Aged, Cohort Studies, Female, Genotype, Hemochromatosis, Hemochromatosis Protein, Heterozygote, Histocompatibility Antigens Class I, Humans, Iron Overload, Male, Membrane Proteins, Middle Aged, Morbidity, Prospective Studies, Time Factors, hereditary disease, iron overload-related disease, liver disease, serum ferritin, transferrin saturation, HealthIron Study Investigators, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background and aimThe risk of hemochromatosis-related morbidity for HFE simple heterozygosity for either the C282Y or H63D substitutions in the HFE protein was assessed using a prospective community-based cohort study.MethodsHFE genotypes were measured for 31,192 persons of northern European descent, aged between 40 and 69 years when recruited to the Melbourne Collaborative Cohort Study, and subjects were followed for an average of 12 years. For a random sample of 1438 participants stratified according to HFE genotype, two sets of biochemical iron indices performed 12 years apart and, at follow-up only, the presence/absence of six disease features associated with hereditary hemochromatosis were obtained. Summary data for 257 (139 female) C282Y simple heterozygotes and 123 (74 female) H63D simple heterozygotes were compared with 330 (181 female) controls with neither HFE mutation.ResultsAt baseline, mean transferrin saturation (TS) (95% confidence interval) and prevalence of TS > 55% were 35.14% (33.25, 37.04) and 3/112 (3%), 33.03% (29.9, 36.15) and 0/39 (0%), and 29.67% (27.93, 31.4) and 3/135 (2%) for C282Y, H63D and wild-type male participants, respectively. At follow-up, mean TS levels remained similar to baseline levels for both men and women irrespective of simple heterozygosity for either mutation. No HFE C282Y or H63D simple heterozygotes had documented iron overload (based on hepatic iron measures or serum ferritin greater than 1000 mg/L at baseline with documented therapeutic venesection).ConclusionNo documented iron overload was observed for HFE simple heterozygotes for either C282Y or H63D, and morbidity for both HFE simple heterozygote groups was similar to that of HFE wild-type participants.

Published
2015

24. Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life

Author

Bui, Dinh S, Lodge, Caroline J, Burgess, John A, Lowe, Adrian J, Perret, Jennifer, Bui, Minh Q, Bowatte, Gayan, Gurrin, Lyle, Johns, David P, Thompson, Bruce R, Hamilton, Garun S, Frith, Peter A, James, Alan L, Thomas, Paul S, Jarvis, Deborah, Svanes, Cecilie, Russell, Melissa, Morrison, Stephen C, Feather, Iain, Allen, Katrina J, Wood-Baker, Richard, Hopper, John, Giles, Graham G, Abramson, Michael J, Walters, Eugene H, Matheson, Melanie C, and Dharmage, Shyamali C

Published
2018
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30. Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial

Author

Ong, Sim Y, Gurrin, Lyle C, Dolling, Lara, Dixon, Jeanette, Nicoll, Amanda J, Wolthuizen, Michelle, Wood, Erica M, Anderson, Gregory J, Ramm, Grant A, Allen, Katrina J, Olynyk, John K, Crawford, Darrell, Ramm, Louise E, Gow, Paul, Durrant, Simon, Powell, Lawrie W, and Delatycki, Martin B

Published
2017
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33. SNP selection for genes of iron metabolism in a study of genetic modifiers of hemochromatosis

Author

Constantine, Clare C, Gurrin, Lyle C, McLaren, Christine E, Bahlo, Melanie, Anderson, Gregory J, Vulpe, Chris D, Forrest, Susan M, Allen, Katrina J, Gertig, Dorota M, and Investigators, HealthIron

Subjects
single-nucleotide polymorphisms, international hapmap project, association, efficiency, maps
Abstract

Background: We report our experience of selecting tag SNPs in 35 genes involved in iron metabolism in a cohort study seeking to discover genetic modifiers of hereditary hemochromatosis. Methods: We combined our own and publicly available resequencing data with HapMap to maximise our coverage to select 384 SNPs in candidate genes suitable for typing on the Illumina platform. Results: Validation/ design scores above 0.6 were not strongly correlated with SNP performance as estimated by Gentrain score. We contrasted results from two tag SNP selection algorithms, LDselect and Tagger. Varying r(2) from 0.5 to 1.0 produced a near linear correlation with the number of tag SNPs required. We examined the pattern of linkage disequilibrium of three levels of resequencing coverage for the transferrin gene and found HapMap phase 1 tag SNPs capture 45% of the >= 3% MAF SNPs found in SeattleSNPs where there is nearly complete resequencing. Resequencing can reveal adjacent SNPs ( within 60 bp) which may affect assay performance. We report the number of SNPs present within the region of six of our larger candidate genes, for different versions of stock genotyping assays. Conclusion: A candidate gene approach should seek to maximise coverage, and this can be improved by adding to HapMap data any available sequencing data. Tag SNP software must be fast and flexible to data changes, since tag SNP selection involves iteration as investigators seek to satisfy the competing demands of coverage within and between populations, and typability on the technology platform chosen.

Published
2008

35. Food Challenge and Community-Reported Reaction Profiles in Food-Allergic Children Aged 1 and 4 Years: A Population-Based Study

Author

Wake, Melissa, Ponsonby, Anne-Louise, Matheson, Melanie, Dwyer, Terry, Prescott, Susan, Robertson, Colin, Zurzolo, Giovanni, Thiele, Leone, Czech, Helen, Shaw, Holly, Anderson, Deborah, Eckert, Jana, Bertalli, Nadine, Sanjeevan, Jeeva, Garner, Carley, Mathers, Megan, Trembath, Kaye, Crawford, Hayley, Chan, Joshua C.K., Peters, Rachel L., Koplin, Jennifer J., Dharmage, Shyamali C., Gurrin, Lyle C., Tang, Mimi L.K., and Allen, Katrina J.

Published
2017
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43. Persistent Food Allergy and Food Allergy Coexistent with Eczema Is Associated with Reduced Growth in the First 4 Years of Life

Author

Robertson, Colin, Hill, David, Vuillermin, Peter, Osborne, Nicholas, Mathers, Megan, Peters, Rachel, Dang, Thanh, Tey, Dean, Robinson, Marnie, Zurzolo, Giovanni, Thiele, Leone, Czech, Helen, Shaw, Holly, Anderson, Deborah, Eckert, Jana, Bertalli, Nadine, Sanjeevan, Jeeva, Tan, Tina, Martin, Pamela, Garner, Carley, Trembath, Kaye, Crawford, Hayley, Suaini, Noor, Ferreira, Manuel, Martino, David, Saffery, Richard, Ellis, Justine, Molloy, John, Brewerton, Maia, Licciardi, Paul, Tilbrook, Kate, Chhabra, Sonia, Beck, Cara, Koplin, Jennifer, Dharmage, Shyamali, Wake, Melissa, Gurrin, Lyle, McWilliam, Vicki, Tang, Mimi, Sun, Cong, Foskey, Rebecca, and Allen, Katrina J.

Published
2016
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44. Polymorphisms affecting vitamin D–binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy

Author

Koplin, Jennifer J., Suaini, Noor H.A., Vuillermin, Peter, Ellis, Justine A., Panjari, Mary, Ponsonby, Anne-Louise, Peters, Rachel L., Matheson, Melanie C., Martino, David, Dang, Thanh, Osborne, Nicholas J., Martin, Pamela, Lowe, Adrian, Gurrin, Lyle C., Tang, Mimi L.K., Wake, Melissa, Dwyer, Terry, Hopper, John, Dharmage, Shyamali C., and Allen, Katrina J.

Published
2016
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