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101. Indications for delivery in pre-eclampsia

Author

Varnier, N, Brown, MA, Reynolds, M, Pettit, F, Davis, G, Mangos, G, Henry, A, Varnier, N, Brown, MA, Reynolds, M, Pettit, F, Davis, G, Mangos, G, and Henry, A

Abstract

Objective: Examine the frequency with which the most accepted indicators for delivery in pre-eclampsia are used in a population with predominantly late-onset (birth > 32 weeks) pre-eclampsia (PE). Methods: Retrospective cohort study using the St George Public Hospital (SGH) Hypertension in Pregnancy database. Demographic, pregnancy, and outcome details were extracted and verified by comparison with data collection sheets. Results: From 2001 to 2013, 908 women (970 babies) with PE were included, of which a subgroup of 303 women (33%) had clearly delineated delivery triggers available. This subgroup of women had similar demographic and outcome characteristics to the total PE population. In this group, the most common maternal trigger for delivery apart from gestational age 37+ weeks was difficult to control/severe hypertension (114 cases, 38%) and the most common fetal trigger intrauterine growth restriction (IUGR: 14 cases, 4%). 78 (35%) of term women had no specific delivery trigger other than gestation. A primary maternal trigger and/or associated complication was slightly more common in those delivering <37 weeks vs 37+ weeks (52 vs 38%, p =.03), while a fetal or combined maternal/fetal complication was over four times more common in preterm women (25 vs 6%, p <.001). Conclusion: In our population of predominantly late-onset PE, maternal triggers for delivery (predominantly severe hypertension) far outweigh fetal triggers (predominantly IUGR). Fetal and mixed indicators for delivery were relatively more common in women delivering preterm, possibly reflecting the severity of placental dysfunction in this subgroup.

Published
2018

102. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Author

Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, Craig, DW, Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, and Craig, DW

Abstract

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.

Published
2018

103. BRCA1 and BRCA2 5′ noncoding region variants identified in breast cancer patients alter promoter activity and protein binding

Author

Burke, LJ, Sevcik, J, Gambino, G, Tudini, E, Mucaki, EJ, Shirley, BC, Whiley, P, Parsons, MT, De Leeneer, K, Gutierrez-Enriquez, S, Santamarina, M, Caputo, SM, dos Santos, ES, Soukupova, J, Janatova, M, Zemankova, P, Lhotova, K, Stolarova, L, Borecka, M, Moles-Fernandez, A, Manoukian, S, Bonanni, B, Edwards, SL, Blok, MJ, Hansen, TVO, Rossing, M, Diez, O, Vega, A, Claes, KBM, Goldgar, DE, Rouleau, E, Radice, P, Peterlongo, P, Rogan, PK, Caligo, M, Spurdle, AB, Brown, MA, Burke, LJ, Sevcik, J, Gambino, G, Tudini, E, Mucaki, EJ, Shirley, BC, Whiley, P, Parsons, MT, De Leeneer, K, Gutierrez-Enriquez, S, Santamarina, M, Caputo, SM, dos Santos, ES, Soukupova, J, Janatova, M, Zemankova, P, Lhotova, K, Stolarova, L, Borecka, M, Moles-Fernandez, A, Manoukian, S, Bonanni, B, Edwards, SL, Blok, MJ, Hansen, TVO, Rossing, M, Diez, O, Vega, A, Claes, KBM, Goldgar, DE, Rouleau, E, Radice, P, Peterlongo, P, Rogan, PK, Caligo, M, Spurdle, AB, and Brown, MA

Abstract

The widespread use of next generation sequencing for clinical testing is detecting an escalating number of variants in noncoding regions of the genome. The clinical significance of the majority of these variants is currently unknown, which presents a significant clinical challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA consortium for sequence variants in the 5' noncoding regions of BC susceptibility genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele frequency < 0.01, 76 of which have not been reported previously. Bioinformatic analysis identified a set of 21 variants most likely to impact transcriptional regulation, and luciferase reporter assays detected altered promoter activity for four of these variants. Electrophoretic mobility shift assays demonstrated that three of these altered the binding of proteins to the respective BRCA1 or BRCA2 promoter regions, including NFYA binding to BRCA1:c.-287C>T and PAX5 binding to BRCA2:c.-296C>T. Clinical classification of variants affecting promoter activity, using existing prediction models, found no evidence to suggest that these variants confer a high risk of disease. Further studies are required to determine if such variation may be associated with a moderate or low risk of BC.

Published
2018

104. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Author

Duffy, DL, Zhu, G, Li, X, Sanna, M, Iles, MM, Jacobs, LC, Evans, DM, Yazar, S, Beesley, J, Law, MH, Kraft, P, Visconti, A, Taylor, JC, Lui, F, Wright, MJ, Henders, AK, Bowdler, L, Glass, D, Ikram, AM, Uitterlinden, AG, Madden, PA, Heath, AC, Nelson, EC, Green, AC, Chanock, S, Barrett, JH, Brown, MA, Hayward, NK, MacGregor, S, Sturm, RA, Hewitt, AW, Kayser, M, Hunter, DJ, Bishop, JAN, Spector, TD, Montgomery, GW, Mackey, DA, Smith, GD, Nijsten, TE, Bishop, DT, Bataille, V, Falchi, M, Han, J, Martins, NG, Duffy, DL, Zhu, G, Li, X, Sanna, M, Iles, MM, Jacobs, LC, Evans, DM, Yazar, S, Beesley, J, Law, MH, Kraft, P, Visconti, A, Taylor, JC, Lui, F, Wright, MJ, Henders, AK, Bowdler, L, Glass, D, Ikram, AM, Uitterlinden, AG, Madden, PA, Heath, AC, Nelson, EC, Green, AC, Chanock, S, Barrett, JH, Brown, MA, Hayward, NK, MacGregor, S, Sturm, RA, Hewitt, AW, Kayser, M, Hunter, DJ, Bishop, JAN, Spector, TD, Montgomery, GW, Mackey, DA, Smith, GD, Nijsten, TE, Bishop, DT, Bataille, V, Falchi, M, Han, J, and Martins, NG

Abstract

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.

Published
2018

105. Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy

Author

Graham, PS, Kaidonis, G, Abhary, S, Gillies, MC, Daniell, M, Essex, RW, Chang, JH, Lake, SR, Pal, B, Jenkins, AJ, Hewitt, AW, Lamoureux, EL, Hykin, PG, Petrovsky, N, Brown, MA, Craig, JE, Burdon, KP, Graham, PS, Kaidonis, G, Abhary, S, Gillies, MC, Daniell, M, Essex, RW, Chang, JH, Lake, SR, Pal, B, Jenkins, AJ, Hewitt, AW, Lamoureux, EL, Hykin, PG, Petrovsky, N, Brown, MA, Craig, JE, and Burdon, KP

Abstract

BACKGROUND: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight-threatening complications of diabetes mellitus and leading causes of adult-onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate complications in Australians of European descent with type 2 diabetes. METHODS: Caucasian Australians with type 2 diabetes were evaluated in a genome-wide association study (GWAS) to compare 270 DME cases and 176 PDR cases with 435 non-retinopathy controls. All participants were genotyped by SNP array and after data cleaning, cases were compared to controls using logistic regression adjusting for relevant covariates. RESULTS: The top ranked SNP for DME was rs1990145 (p = 4.10 × 10- 6, OR = 2.02 95%CI [1.50, 2.72]) on chromosome 2. The top-ranked SNP for PDR was rs918519 (p = 3.87 × 10- 6, OR = 0.35 95%CI [0.22, 0.54]) on chromosome 5. A trend towards association was also detected at two SNPs reported in the only other reported GWAS of DR in Caucasians; rs12267418 near MALRD1 (p = 0.008) in the DME cohort and rs16999051 in the diabetes gene PCSK2 (p = 0.007) in the PDR cohort. CONCLUSION: This study has identified loci of interest for DME and PDR, two common ocular complications of diabetes. These findings require replication in other Caucasian cohorts with type 2 diabetes and larger cohorts will be required to identify genetic loci with statistical confidence. There is considerable overlap in the patient cohorts with each retinopathy subtype, complicating the search for genes that contribute to PDR and DME biology.

Published
2018

106. Longitudinal expression profiling of CD4+and CD8+cells in patients with active to quiescent giant cell arteritis

Author

De Smit, E, Lukowski, SW, Anderson, L, Senabouth, A, Dauyey, K, Song, S, Wyse, B, Wheeler, L, Chen, CY, Cao, K, Ten Yuen, AW, Shuey, N, Clarke, L, Sanchez, IL, Hung, SSC, Pebay, A, Mackey, DA, Brown, MA, Hewitt, AW, Powell, JE, De Smit, E, Lukowski, SW, Anderson, L, Senabouth, A, Dauyey, K, Song, S, Wyse, B, Wheeler, L, Chen, CY, Cao, K, Ten Yuen, AW, Shuey, N, Clarke, L, Sanchez, IL, Hung, SSC, Pebay, A, Mackey, DA, Brown, MA, Hewitt, AW, and Powell, JE

Abstract

BACKGROUND: Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA. METHODS: We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls. RESULTS: Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months. CONCLUSIONS: This is the first longitudinal gene expression study undertaken to identify

Published
2018

107. Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

Author

Leo, PJ, Madeleine, MM, Wang, S, Schwartz, SM, Newell, F, Pettersson-Kymmer, U, Hemminki, K, Hallmans, G, Tiews, S, Steinberg, W, Rader, JS, Castro, F, Safaeian, M, Franco, EL, Coutlée, F, Ohlsson, C, Cortes, A, Marshall, M, Mukhopadhyay, P, Cremin, K, Johnson, LG, Trimble, CL, Garland, S, Tabrizi, SN, Wentzensen, N, Sitas, F, Little, J, Cruickshank, M, Frazer, IH, Hildesheim, A, Brown, MA, Leo, PJ, Madeleine, MM, Wang, S, Schwartz, SM, Newell, F, Pettersson-Kymmer, U, Hemminki, K, Hallmans, G, Tiews, S, Steinberg, W, Rader, JS, Castro, F, Safaeian, M, Franco, EL, Coutlée, F, Ohlsson, C, Cortes, A, Marshall, M, Mukhopadhyay, P, Cremin, K, Johnson, LG, Trimble, CL, Garland, S, Tabrizi, SN, Wentzensen, N, Sitas, F, Little, J, Cruickshank, M, Frazer, IH, Hildesheim, A, and Brown, MA

Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].

Published
2018

108. MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer.

Author

Milevskiy, MJG, Sandhu, GK, Wronski, A, Korbie, D, Brewster, BL, Shewan, A, Edwards, SL, French, JD, Brown, MA, Milevskiy, MJG, Sandhu, GK, Wronski, A, Korbie, D, Brewster, BL, Shewan, A, Edwards, SL, French, JD, and Brown, MA

Abstract

Depletion of BRCA1 protein in mouse mammary glands results in defects in lactational development and increased susceptibility to mammary cancer. Extensive work has focussed on the role of BRCA1 in the normal breast and in the development of breast cancer, the cell of origin for BRCA1 tumours and the protein-coding genes altered in BRCA1 deficient cells. However, the role of non-coding RNAs in BRCA1-deficient cells is poorly understood. To evaluate miRNA expression in BRCA1 deficient mammary cells, RNA sequencing was performed on the mammary glands of Brca1 knockout mice. We identified 140 differentially expressed miRNAs, 9 of which were also differentially expressed in human BRCA1 breast tumours or familial non-BRCA1 patients and during normal gland development. We show that BRCA1 binds to putative cis-elements in promoter regions of the miRNAs with the potential to regulate their expression, and that four miRNAs (miR-29b-1-5p, miR-664, miR-16-2 and miR-744) significantly stratified the overall survival of basal-like tumours. Importantly the prognostic value of miR-29b-1-5p was higher in significance than several commonly used clinical biomarkers. These results emphasise the role of Brca1 in modulating expression of miRNAs and highlights the potential for BRCA1 regulated miRNAs to be informative biomarkers associated with BRCA1 loss and survival in breast cancer.

Published
2018

109. Genetic Variants in ERAP1 and ERAP2 Associated With Immune-Mediated Diseases Influence Protein Expression and the Isoform Profile

Author

Hanson, AL, Cuddihy, T, Haynes, K, Loo, D, Morton, CJ, Oppermann, U, Leo, P, Thomas, GP, Kim-Anh, LC, Kenna, TJ, Brown, MA, Hanson, AL, Cuddihy, T, Haynes, K, Loo, D, Morton, CJ, Oppermann, U, Leo, P, Thomas, GP, Kim-Anh, LC, Kenna, TJ, and Brown, MA

Abstract

OBJECTIVE: Endoplasmic reticulum aminopeptidase 1 (ERAP-1) and ERAP-2, encoded on chromosome 5q15, trim endogenous peptides for HLA-mediated presentation to the immune system. Polymorphisms in ERAP1 and/or ERAP2 are strongly associated with several immune-mediated diseases with specific HLA backgrounds, implicating altered peptide handling and presentation as prerequisites for autoreactivity against an arthritogenic peptide. Given the thorough characterization of disease risk-associated polymorphisms that alter ERAP activity, this study aimed instead to interrogate the expression effect of chromosome 5q15 polymorphisms to determine their effect on ERAP isoform and protein expression. METHODS: RNA sequencing and genotyping across chromosome 5q15 were performed to detect genetic variants in ERAP1 and ERAP2 associated with altered total gene and isoform-specific expression. The functional implication of a putative messenger RNA splice-altering variant on ERAP-1 protein levels was validated using mass spectrometry. RESULTS: Polymorphisms associated with ankylosing spondylitis (AS) significantly influenced the transcript and protein expression of ERAP-1 and ERAP-2. Disease risk-associated polymorphisms in and around both genes were also associated with increased gene expression. Furthermore, key risk-associated ERAP1 variants were associated with altered transcript splicing, leading to allele-dependent alternate expression of 2 distinct isoforms and significant differences in the type of ERAP-1 protein produced. CONCLUSION: In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression of ERAP1 and ERAP2 supports the notion of using aminopeptidase inhibition to treat AS and other ERAP-associated conditions.

Published
2018

110. Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

Author

Ghoussaini, M, Edwards, SL, Michailidou, K, Nord, S, Cowper-Sal Lari, R, Desai, K, Kar, S, Hillman, KM, Kaufmann, S, Glubb, DM, Beesley, J, Dennis, J, Bolla, MK, Wang, Q, Dicks, E, Guo, Q, Schmidt, MK, Shah, M, Luben, R, Brown, J, Czene, K, Darabi, H, Eriksson, M, Klevebring, D, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Lambrechts, D, Thienpont, B, Neven, P, Wildiers, H, Broeks, A, Van't Veer, LJ, Rutgers, EJT, Couch, FJ, Olson, JE, Hallberg, E, Vachon, C, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Peto, J, Dos-Santos-Silva, I, Gibson, L, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Hall, P, Li, J, Liu, J, Humphreys, K, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Matsuo, K, Ito, H, Iwata, H, Yatabe, Y, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Wu, AH, Tseng, C-C, Van Den Berg, D, Stram, DO, Benitez, J, Pilar Zamora, M, Perez, JIA, Menéndez, P, Shu, X-O, Lu, W, Gao, Y-T, Cai, Q, Cox, A, Cross, SS, Reed, MWR, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Lindblom, A, Margolin, S, Teo, SH, Yip, CH, Lee, DSC, Wong, TY, Hooning, MJ, Martens, JWM, Collée, JM, van Deurzen, CHM, Hopper, JL, Southey, MC, Tsimiklis, H, Kapuscinski, MK, Shen, C-Y, Wu, P-E, Yu, J-C, Chen, S-T, Alnæs, GG, Borresen-Dale, A-L, Giles, GG, Milne, RL, McLean, C, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Hartman, M, Miao, H, Buhari, SABS, Teo, YY, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, MJ, García-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Brauch, H, Brüning, T, Koto, Y-D, Radice, P, Peterlongo, P, Bonanni, B, Volorio, S, Dörk, T, Bogdanova, NV, Helbig, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Hamann, U, Torres, D, Zheng, W, Long, J, Anton-Culver, H, Neuhausen, SL, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, CS, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, de Santiago, I, Carroll, J, Caldas, C, Brown, MA, Lupien, M, Kristensen, VN, Pharoah, PDP, Chenevix-Trench, G, French, JD, Easton, DF, Dunning, AM, Ghoussaini, M, Edwards, SL, Michailidou, K, Nord, S, Cowper-Sal Lari, R, Desai, K, Kar, S, Hillman, KM, Kaufmann, S, Glubb, DM, Beesley, J, Dennis, J, Bolla, MK, Wang, Q, Dicks, E, Guo, Q, Schmidt, MK, Shah, M, Luben, R, Brown, J, Czene, K, Darabi, H, Eriksson, M, Klevebring, D, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Lambrechts, D, Thienpont, B, Neven, P, Wildiers, H, Broeks, A, Van't Veer, LJ, Rutgers, EJT, Couch, FJ, Olson, JE, Hallberg, E, Vachon, C, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Peto, J, Dos-Santos-Silva, I, Gibson, L, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Hall, P, Li, J, Liu, J, Humphreys, K, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Matsuo, K, Ito, H, Iwata, H, Yatabe, Y, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Wu, AH, Tseng, C-C, Van Den Berg, D, Stram, DO, Benitez, J, Pilar Zamora, M, Perez, JIA, Menéndez, P, Shu, X-O, Lu, W, Gao, Y-T, Cai, Q, Cox, A, Cross, SS, Reed, MWR, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Lindblom, A, Margolin, S, Teo, SH, Yip, CH, Lee, DSC, Wong, TY, Hooning, MJ, Martens, JWM, Collée, JM, van Deurzen, CHM, Hopper, JL, Southey, MC, Tsimiklis, H, Kapuscinski, MK, Shen, C-Y, Wu, P-E, Yu, J-C, Chen, S-T, Alnæs, GG, Borresen-Dale, A-L, Giles, GG, Milne, RL, McLean, C, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Hartman, M, Miao, H, Buhari, SABS, Teo, YY, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, MJ, García-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Brauch, H, Brüning, T, Koto, Y-D, Radice, P, Peterlongo, P, Bonanni, B, Volorio, S, Dörk, T, Bogdanova, NV, Helbig, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Hamann, U, Torres, D, Zheng, W, Long, J, Anton-Culver, H, Neuhausen, SL, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, CS, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, de Santiago, I, Carroll, J, Caldas, C, Brown, MA, Lupien, M, Kristensen, VN, Pharoah, PDP, Chenevix-Trench, G, French, JD, Easton, DF, and Dunning, AM

Abstract

This corrects the article DOI: 10.1038/ncomms5999.

Published
2018

111. Rare variants in Fanconi anemia genes are enriched in acute myeloid leukemia

Author

Maung, KZY, Leo, PJ, Bassal, M, Casolari, DA, Gray, JX, Bray, SC, Pederson, S, Singhal, D, Samaraweera, SE, Tran, N, Cildir, G, Marshall, M, Ewing, A, Duncan, EL, Brown, MA, Saal, R, Tergaonkar, V, To, LB, Marlton, P, Gill, D, Lewis, I, Deans, AJ, Brown, AL, D'Andrea, RJ, Gonda, TJ, Maung, KZY, Leo, PJ, Bassal, M, Casolari, DA, Gray, JX, Bray, SC, Pederson, S, Singhal, D, Samaraweera, SE, Tran, N, Cildir, G, Marshall, M, Ewing, A, Duncan, EL, Brown, MA, Saal, R, Tergaonkar, V, To, LB, Marlton, P, Gill, D, Lewis, I, Deans, AJ, Brown, AL, D'Andrea, RJ, and Gonda, TJ

Published
2018

115. The F158V polymorphism in FcγRIIIA shows disparate associations with rheumatoid arthritis in two genetically distinct populations. (Concise Report)

Author

Milicic, A, Misra, R, Agrawal, S, Aggarwal, A, Brown, MA, and Wordsworth, BP

Subjects
Medical genetics -- Research, Rheumatoid arthritis -- Genetic aspects -- Research, Health
Abstract

Objectives: To investigate the association of the FcγRIIIA gene with rheumatoid arthritis (RA) in two genetically distinct groups: a white group from the United Kingdom and a northern Indian group. [...]

Published
2002

116. Genetic testing for haemochromatosis in patients with chondrocalcinosis. (Concise Report)

Author

Timms, AE, Sathananthan, R, Bradbury, L, Athanasou, NA, and Brown, MA

Subjects
Genetic disorders -- Diagnosis -- Genetic aspects, Hemochromatosis -- Diagnosis -- Genetic aspects, Chondrocalcinosis -- Genetic aspects -- Diagnosis, Health, Diagnosis, Genetic aspects
Abstract

Hereditary haemochromatosis (HH) is the most common lethal monogenic human disease, affecting roughly 1 in 300 white northern Europeans. Homozygosity for the C282Y polymorphism within the HFE gene causes more [...]

Published
2002

117. Postpartum physiology, psychology and paediatric follow up study (P4 Study) – Study protocol

Author

Davis, GK, Roberts, L, Mangos, G, Henry, A, Pettit, F, O'Sullivan, A, Homer, CSE, Craig, M, Harvey, SB, and Brown, MA

Subjects
Depression, Postpartum Period, Child Behavior, Infant, Blood Pressure, Hypertension, Pregnancy-Induced, Anxiety, Kidney, Stress Disorders, Post-Traumatic, Child Development, Vascular Stiffness, Liver, Pre-Eclampsia, Pregnancy, Research Design, Case-Control Studies, Child, Preschool, Body Composition, Blood Vessels, Humans, Ventricular Function, Female, Prospective Studies, Compliance
Abstract

© 2016 International Society for the Study of Hypertension in Pregnancy Background Women who have had hypertension in pregnancy are at greater risk of long term cardiovascular disease (CVD). Little is known about their cardiovascular risk postpartum or the effects on the woman's mental health and the outcomes of their infants. In this project we will study the physiological and psychological health of women and the physical health and development of their infants six months, two years and five years after birth. We will establish normal blood pressure (BP) and metabolic function for women who were normotensive in pregnancy and use these to assess women who had gestational hypertension (GH) or preeclampsia (PE). Design/methods Women will be asked to participate if they have given birth in the preceding six months. They will be excluded if they had diabetes, hypertension, renal or other serious maternal disease prior to pregnancy or congenital anomaly in the pregnancy. We will recruit 292 women who were normotensive and their babies, 100 who had GH and 100 who had PE and their babies. They will be assessed at six months, two and five years after birth. At each assessment mothers will have their blood pressure (BP) assessed peripherally with a liquid crystal sphygmomanometer and 24 h ambulatory blood pressure monitoring (ABPM), and centrally with non-invasive applanation tonometry. Additional physiological testing will include: body composition; energy balance; vascular compliance; cardiac function; liver and renal function, lipids and biochemistry; glucose and insulin; and urinalysis. Psychological status will be assessed with validated self-report questionnaires for depression, anxiety, post-traumatic stress disorder (PTSD) and mother-infant bonding. The babies will have a medical examination by a paediatrician at each assessment. Their behavioural development will be assessed with an Ages and Stages Questionnaire completed by their mother at each assessment and a developmental assessment by a child psychologist at two and five years. Conclusions This study will re-define normal BP and other physiological parameters for young parous women thereby permitting a more sensitive assessment of post-partum BP and other cardiovascular risk markers in women who have had GH or PE. It will also determine the extent, if any, of psychological disorders in these women and developmental or other concerns in their babies. Trials registration Australian and New Zealand Clinical Trials Registry Number: ACTRN12613001260718.

Published
2016

122. HLA-DR/DQ haplotype in rheumatoid arthritis: novel allelic associations in UK Caucasians

Author

Milicic, A, Lee, D, Brown, MA, Darke, C, and Wordsworth, BP

Subjects
musculoskeletal diseases, skin and connective tissue diseases
Abstract

OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). METHODS: HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. RESULTS: Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRbeta molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. CONCLUSION: These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.

Published
2016

123. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators

Author

White, HD, Aylward, PE, Frey, MJ, Adgey, AA, Nair, R, Hillis, WS, Shalev, Y, Brown, MA, French, JK, Collins, R, Maraganore, J, and Adelman, B

Abstract

BACKGROUND: Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. METHODS AND RESULTS: Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P

Published
2016

131. Genome-Wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

Author

Strange, A, Riley, BP, Spencer, CCA, Morris, DW, Pirinen, M, O'Dushlaine, CT, Su, Z, Maher, BS, Freeman, C, Cormican, P, Bellenguez, C, Kenny, EM, Band, G, Wormley, B, Donohoe, G, Dilthey, A, Moutsianas, L, Quinn, E, Edkins, S, Judge, R, Coleman, K, Hunt, S, Tropea, D, Roche, S, Cummings, L, Kelleher, E, McKeon, P, Dinan, T, McDonald, C, Murphy, KC, O'Callaghan, E, O'Neill, FA, Waddington, JL, Walsh, D, Giannoulatou, E, Langford, C, Deloukas, P, Gray, E, Dronov, S, Potter, S, Pearson, R, Vukcevic, D, Tashakkori-Ghanbaria, A, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Stone, J, Scolnick, E, Purcell, S, Sklar, P, Ripke, S, Walters, J, Owen, MJ, O'Donovan, MC, Peltonen, L, McVean, G, Kendler, KS, Gill, M, Donnelly, P, Corvin, A, Conso, ISG, Consortium, SGENE, Psychiat, SWG, and Consor, WTCC

Subjects
Adult, Male, Genotype, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, HLA-C Antigens, Major histocompatibility complex, Polymorphism, Single Nucleotide, Article, HLA-C, Calcium Channels, T-Type, Young Adult, Risk Factors, Databases, Genetic, tourette-syndrome, SNP, Humans, genetics, Genetic Predisposition to Disease, Allele, gene, Biological Psychiatry, Aged, Genetics, cacna1i, breakpoint, Aged, 80 and over, biology, deletions, polygene score, classical hla alleles, Middle Aged, hlac, major histocompatibility complex, disruption, biology.protein, Schizophrenia, Female, immp2l, Ireland, Genome-Wide Association Study
Abstract

BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.

Published
2016

132. Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians

Author

Milicic, A, Brown, MA, and Wordsworth, BP

Subjects
chemical and pharmacologic phenomena
Abstract

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

Published
2016

133. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Author

Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M

Subjects
Linkage disequilibrium, Multiple Sclerosis, Genotype, Population, Single-nucleotide polymorphism, Genome-wide association study, Autoimmunity, Breast Neoplasms, Biology, medicine.disease_cause, Aminopeptidases, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Minor Histocompatibility Antigens, Genetics, medicine, Humans, Spondylitis, Ankylosing, Receptors, Immunologic, education, Genetic association, education.field_of_study, Ankylosing spondylitis, Thyroiditis, Autoimmune, Chromosome Mapping, Receptors, Interleukin, medicine.disease, Endoplasmic reticulum aminopeptidase 2, Genetics, Population, Haplotypes, Case-Control Studies, Immunology, North America
Abstract

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Published
2016
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