Showing papers by "Florence Demenais published in 2018"
Florence Demenais1, Florence Demenais2, Patricia Margaritte-Jeannin1, Patricia Margaritte-Jeannin2 +213 more•Institutions (79)
TL;DR: A meta-analysis of GWAS studies for asthma from multiancestral cohorts identifies five new loci and finds that the asthma-associated loci are enriched near enhancer marks in immune cells, suggesting a major role of these loci in the regulation of immunologically related mechanisms.
Abstract: We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
363 citations
03 Feb 2018
281 citations
King's College London1, QIMR Berghofer Medical Research Institute2, Beijing Institute of Genomics3, Erasmus University Rotterdam4, Chinese Academy of Sciences5, Indiana University – Purdue University Indianapolis6, University of Leeds7, French Institute of Health and Medical Research8, Paris Diderot University9, Brigham and Women's Hospital10, The Hertz Corporation11
TL;DR: A large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry identifies significant association with tanning ability at 20 loci and suggests that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma, might act on disease risk through modulation ofTanning ability.
Abstract: The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.
74 citations
King's College London1, QIMR Berghofer Medical Research Institute2, Beijing Institute of Genomics3, Erasmus University Rotterdam4, Chinese Academy of Sciences5, Indiana University – Purdue University Indianapolis6, University of Leeds7, French Institute of Health and Medical Research8, Paris Diderot University9, Brigham and Women's Hospital10, The Hertz Corporation11
TL;DR: This paper reported a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry and identified significant association with tanning ability at 20 loci.
Abstract: The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.
59 citations
TL;DR: Gene variants in the pigmentation pathway, particularly MC1R, were responsible for most of the incremental improvement, and testing of genomic variants can identify people who are susceptible to melanoma despite not having a traditional phenotypic risk profile.
49 citations
TL;DR: This work proposes to integrate the genome and exposome data in what is presented as the exposomesome-genome paradigm, to help strengthen approaches to identify relevant predictive markers that can support precise prevention actions both at the population and at the individual levels.
33 citations
TL;DR: A potential key role of genes at the identified porcine loci in tumor invasion and immune response modulation of the progression phenotypes of spontaneous melanoma are revealed and can open new routes for future melanoma research in humans.
Abstract: Despite major advances, it is estimated that a large part of melanoma predisposing genes remains to be discovered. Animal models of spontaneous diseases are valuable tools and experimental crosses can be used to identify and fine-map new susceptibility loci associated with melanoma. We performed a Genome-Wide Association Study (GWAS) of melanoma occurrence and progression (clinical ulceration and presence of metastasis) in a porcine model of spontaneous melanoma, the MeLiM pig. Five loci on chromosomes 2, 5, 7, 8 and 16 showed genome-wide significant associations (p < 5 × 10-6) with either one of these phenotypes. Suggestive associations (p < 5 × 10-5) were also found at 16 additional loci. Moreover, comparison of the porcine results to those reported by human melanoma GWAS indicated shared association signals notably at CDKAL1 and TERT loci but also nearby CCND1, FTO, PLA2G6 and TMEM38B-RAD23B loci. Extensive search of the literature revealed a potential key role of genes at the identified porcine loci in tumor invasion (DST, PLEKHA5, CBY1, LIMK2 and ETV5) and immune response modulation (ETV5, HERC3 and DICER1) of the progression phenotypes. These biological processes are consistent with the clinico-pathological features of MeLiM tumors and can open new routes for future melanoma research in humans.
12 citations
TL;DR: Genetic studies of eczema have identified many genes, which explain only 14% of the heritability, but which may be partly due to ignored gene–gene (G‐G) interactions.
Abstract: Background Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored gene-gene (G-G) interactions. Objective Our aim was to detect new interacting genes involved in eczema. Methods The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families. Results One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P = 1.1 × 10-8 under the significant threshold of 10-7 ). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P = 4 × 10-8 under the significant threshold of 4 × 10-6 ) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects. Conclusion This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility. Further confirmation of this interaction as well as functional studies is needed to better understand the role of these genes in eczema.
7 citations
TL;DR: This paper presents a meta-analysis of 120 cases of central giant cell granuloma located in Switzerland over a 12-year period and shows clear patterns of prognosis for meningitis and organ prolapse in women.
Abstract: 1INSERM U946, Genetic Variation and Human Diseases Unit; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie Paris (France), 2Population Health Sciences, Bristol Medical School, University of Bristol Bristol (United Kingdom), 3Dr von Hauner Children's Hospital, Ludwig Maximilian University; Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research Munich (Germany), 4Research Institute of Medical Genetics, Tomsk NRMC Tomsk (Russian Fed.), 5Swiss Tropical and Public Health Institute; University of Basel Basel (Switzerland), 6Busselton Population Medical Research Institute, Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital; School of Population Health, University of Western Australia Nedlands (Australia), 7Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College; MRC-PHE Centre for Environment & Health London (United Kingdom), 8Institute of Biochemistry and Genetics Subdivision of the Ufa Federal Research Center of the Russian Academy of Science; Bashkir State University, Department of Genetics and Fundamental Medicine Ufa (Russian Fed.), 9Département des sciences fondamentales, Université du Québec à Chicoutimi Saguenay (Canada), 10Siberian State Medical University Tomsk (Russian Fed.), 11Inserm, Unit 700, Team of Epidemiology; Université Paris-Diderot Paris 7 Paris (France)
2 citations
TL;DR: This paper presents a meta-analysis of 120 cases of Clostridium difficile associated with septicaemia in eight francophone countries over a 25-year period (1995-2002) and shows clear patterns of decline in the number of cases diagnosed with these diseases and their severity.
Abstract: 1Inserm, UMR-946, Genetic Variation and Human Diseases Unit; Université Paris Diderot; Université Pierre et Marie Curie Paris (France), 2Inserm, UMR-946, Genetic Variation and Human Diseases Unit; Université Paris Diderot Paris (France), 3Population Health Sciences, Bristol Medical School, University of Bristol Bristol (United Kingdom), 4Département des sciences fondamentales, Université du Québec à Chicoutimi; Centre intégré universitaire de santé et de services sociaux du Saguenay–Lac-Saint-Jean Chicoutimi (Canada), 5Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College; MRC-PHE Centre for Environment & Health London (United Kingdom), 6Dr von Hauner Children's Hospital, Ludwig Maximilian University; Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research Munich (Germany), 7ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Municipal Institute of Medical Research (IMIM-Hospital del Mar) Barcelona (Spain)
1 citations