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1. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Author

Joshua C Randall, Thomas W Winkler, Zoltán Kutalik, Sonja I Berndt, Anne U Jackson, Keri L Monda, Tuomas O Kilpeläinen, Tõnu Esko, Reedik Mägi, Shengxu Li, Tsegaselassie Workalemahu, Mary F Feitosa, Damien C Croteau-Chonka, Felix R Day, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Adam E Locke, Iain Mathieson, Andre Scherag, Sailaja Vedantam, Andrew R Wood, Liming Liang, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Emmanouil T Dermitzakis, Antigone S Dimas, Fredrik Karpe, Josine L Min, George Nicholson, Deborah J Clegg, Thomas Person, Jon P Krohn, Sabrina Bauer, Christa Buechler, Kristina Eisinger, DIAGRAM Consortium, Amélie Bonnefond, Philippe Froguel, MAGIC Investigators, Jouke-Jan Hottenga, Inga Prokopenko, Lindsay L Waite, Tamara B Harris, Albert Vernon Smith, Alan R Shuldiner, Wendy L McArdle, Mark J Caulfield, Patricia B Munroe, Henrik Grönberg, Yii-Der Ida Chen, Guo Li, Jacques S Beckmann, Toby Johnson, Unnur Thorsteinsdottir, Maris Teder-Laving, Kay-Tee Khaw, Nicholas J Wareham, Jing Hua Zhao, Najaf Amin, Ben A Oostra, Aldi T Kraja, Michael A Province, L Adrienne Cupples, Nancy L Heard-Costa, Jaakko Kaprio, Samuli Ripatti, Ida Surakka, Francis S Collins, Jouko Saramies, Jaakko Tuomilehto, Antti Jula, Veikko Salomaa, Jeanette Erdmann, Christian Hengstenberg, Christina Loley, Heribert Schunkert, Claudia Lamina, H Erich Wichmann, Eva Albrecht, Christian Gieger, Andrew A Hicks, Asa Johansson, Peter P Pramstaller, Sekar Kathiresan, Elizabeth K Speliotes, Brenda Penninx, Anna-Liisa Hartikainen, Marjo-Riitta Jarvelin, Ulf Gyllensten, Dorret I Boomsma, Harry Campbell, James F Wilson, Stephen J Chanock, Martin Farrall, Anuj Goel, Carolina Medina-Gomez, Fernando Rivadeneira, Karol Estrada, André G Uitterlinden, Albert Hofman, M Carola Zillikens, Martin den Heijer, Lambertus A Kiemeney, Andrea Maschio, Per Hall, Jonathan Tyrer, Alexander Teumer, Henry Völzke, Peter Kovacs, Anke Tönjes, Massimo Mangino, Tim D Spector, Caroline Hayward, Igor Rudan, Alistair S Hall, Nilesh J Samani, Antony Paul Attwood, Jennifer G Sambrook, Joseph Hung, Lyle J Palmer, Marja-Liisa Lokki, Juha Sinisalo, Gabrielle Boucher, Heikki Huikuri, Mattias Lorentzon, Claes Ohlsson, Niina Eklund, Johan G Eriksson, Cristina Barlassina, Carlo Rivolta, Ilja M Nolte, Harold Snieder, Melanie M Van der Klauw, Jana V Van Vliet-Ostaptchouk, Pablo V Gejman, Jianxin Shi, Kevin B Jacobs, Zhaoming Wang, Stephan J L Bakker, Irene Mateo Leach, Gerjan Navis, Pim van der Harst, Nicholas G Martin, Sarah E Medland, Grant W Montgomery, Jian Yang, Daniel I Chasman, Paul M Ridker, Lynda M Rose, Terho Lehtimäki, Olli Raitakari, Devin Absher, Carlos Iribarren, Hanneke Basart, Kees G Hovingh, Elina Hyppönen, Chris Power, Denise Anderson, John P Beilby, Jennie Hui, Jennifer Jolley, Hendrik Sager, Stefan R Bornstein, Peter E H Schwarz, Kati Kristiansson, Markus Perola, Jaana Lindström, Amy J Swift, Matti Uusitupa, Mustafa Atalay, Timo A Lakka, Rainer Rauramaa, Jennifer L Bolton, Gerry Fowkes, Ross M Fraser, Jackie F Price, Krista Fischer, Kaarel Krjutå Kov, Andres Metspalu, Evelin Mihailov, Claudia Langenberg, Jian'an Luan, Ken K Ong, Peter S Chines, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Sarah Edkins, Paul W Franks, Göran Hallmans, Dmitry Shungin, Andrew David Morris, Colin N A Palmer, Raimund Erbel, Susanne Moebus, Markus M Nöthen, Sonali Pechlivanis, Kristian Hveem, Narisu Narisu, Anders Hamsten, Steve E Humphries, Rona J Strawbridge, Elena Tremoli, Harald Grallert, Barbara Thorand, Thomas Illig, Wolfgang Koenig, Martina Müller-Nurasyid, Annette Peters, Bernhard O Boehm, Marcus E Kleber, Winfried März, Bernhard R Winkelmann, Johanna Kuusisto, Markku Laakso, Dominique Arveiler, Giancarlo Cesana, Kari Kuulasmaa, Jarmo Virtamo, John W G Yarnell, Diana Kuh, Andrew Wong, Lars Lind, Ulf de Faire, Bruna Gigante, Patrik K E Magnusson, Nancy L Pedersen, George Dedoussis, Maria Dimitriou, Genovefa Kolovou, Stavroula Kanoni, Kathleen Stirrups, Lori L Bonnycastle, Inger Njølstad, Tom Wilsgaard, Andrea Ganna, Emil Rehnberg, Aroon Hingorani, Mika Kivimaki, Meena Kumari, Themistocles L Assimes, Inês Barroso, Michael Boehnke, Ingrid B Borecki, Panos Deloukas, Caroline S Fox, Timothy Frayling, Leif C Groop, Talin Haritunians, David Hunter, Erik Ingelsson, Robert Kaplan, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Gonçalo R Abecasis, Mark I McCarthy, Joel N Hirschhorn, Lu Qi, Ruth J F Loos, Cecilia M Lindgren, Kari E North, and Iris M Heid

Subjects
Genetics, QH426-470
Abstract

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR

Published
2013
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2. Genetic Variation in the Social Environment Contributes to Health and Disease

Author

Jesse Ingels, Jon P. Krohn, Jacques Callebert, Robert W. Williams, Amelie Baud, Jean-Marie Launay, Megan K. Mulligan, Andres Legarra, Casey J. Bohl, Francesco Paolo Casale, Oliver Stegle, European Mol Biol Lab, Wellcome Genome Campus, European Bioinformatics Institute, Dept Genet Genom & Informat, Hlth Sci Ctr, University of Tennessee System, U942, Hop Lariboisiere, AP HP,Dept Biochem, Institut National de la Santé et de la Recherche Médicale (INSERM), Wellcome Trust Centre for Human Genetics, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]

Subjects
0301 basic medicine, Cancer Research, Heredity, Genetic Linkage, [SDV]Life Sciences [q-bio], Social Sciences, Social Environment, medicine.disease_cause, Mice, Sociology, Missing heritability problem, Psychology, Gene–environment interaction, Genetics (clinical), Genetics, Mammalian Genomics, Social Research, Animal Behavior, Genomics, Phenotypes, Mice, Inbred DBA, Animal Sociality, Perspective, Genotype, lcsh:QH426-470, Biology, Quantitative trait locus, Interpersonal Relationships, 03 medical and health sciences, Quantitative Trait, Heritable, Genetic variation, medicine, Animals, Genetic Predisposition to Disease, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Wound Healing, Behavior, Body Weight, Immunity, Genetic Variation, Biology and Life Sciences, Social environment, Human Genetics, Heritability, Mice, Inbred C57BL, lcsh:Genetics, Collective Human Behavior, 030104 developmental biology, Animal Genomics, Epistasis, Gene-Environment Interaction, Zoology
Abstract

Assessing the impact of the social environment on health and disease is challenging. As social effects are in part determined by the genetic makeup of social partners, they can be studied from associations between genotypes of one individual and phenotype of another (social genetic effects, SGE, also called indirect genetic effects). For the first time we quantified the contribution of SGE to more than 100 organismal phenotypes and genome-wide gene expression measured in laboratory mice. We find that genetic variation in cage mates (i.e. SGE) contributes to variation in organismal and molecular measures related to anxiety, wound healing, immune function, and body weight. Social genetic effects explained up to 29% of phenotypic variance, and for several traits their contribution exceeded that of direct genetic effects (effects of an individual's genotypes on its own phenotype). Importantly, we show that ignoring SGE can severely bias estimates of direct genetic effects (heritability). Thus SGE may be an important source of "missing heritability" in studies of complex traits in human populations. In summary, our study uncovers an important contribution of the social environment to phenotypic variation, sets the basis for using SGE to dissect social effects, and identifies an opportunity to improve studies of direct genetic effects.

Published
2017

3. A comparison of exogenous promoter activity at the ROSA26 locus using a PhiC31 integrase mediated cassette exchange approach in mouse es cells

Author

Benjamin Davies, Chiann-mun Chen, Jon P. Krohn, and Shoumo Bhattacharya

Subjects
RNA, Untranslated, lcsh:Medicine, Gene Expression, Mice, 0302 clinical medicine, Genes, Reporter, Molecular Cell Biology, Bacteriophages, lcsh:Science, Luciferases, Promoter Regions, Genetic, Genetics, Recombination, Genetic, 0303 health sciences, Multidisciplinary, biology, Genetically Modified Organisms, Stem Cells, Transfection, Cell biology, Integrase, Cellular Types, Genetic Engineering, Research Article, Biotechnology, Transgene, Genetic Vectors, Mutagenesis (molecular biology technique), Context (language use), Cell Line, 03 medical and health sciences, Animals, Humans, Gene, Biology, Embryonic Stem Cells, 030304 developmental biology, Integrases, lcsh:R, Chromosomal Position Effects, Proteins, Promoter, Mutagenesis, Insertional, Genetic Loci, biology.protein, lcsh:Q, 030217 neurology & neurosurgery, Transgenics, Developmental Biology
Abstract

The activities of nine ubiquitous promoters (ROSA26, CAG, CMV, CMVd1, UbC, EF1α, PGK, chicken β-actin and MC1) have been quantified and compared in mouse embryonic stem cells. To avoid the high variation in transgene expression which results from uncontrolled copy number and chromosomal position effects when using random insertion based transgenic approaches, we have adopted a PhiC31 integrase mediated cassette exchange method for the efficient insertion of transgenes at single copy within a defined and well characterized chromosomal position, ROSA26. This has enabled the direct comparison of constructs from within the same genomic context and allows a systematic and quantitative assessment of the strengths of the promoters in comparison with the endogenous ROSA26 promoter. The behavior of these exogenous promoters, when integrated at ROSA26 in both sense and antisense orientations, reveals a large variation in their levels of activity. In addition, a subset of promoters, EF1α, UbC and CAG, show an increased activity in the sense orientation as a consequence of integration. Transient transfection experiments confirmed these observations to reflect integration dependent effects and also revealed significant differences in the behaviour of these promoters when delivered transiently or stably. As well as providing an important reference which will facilitate the choice of an appropriate promoter to achieve the desired level of expression for a specific research question, this study also demonstrates the suitability of the cassette exchange methodology for the robust and reliable expression of multiple variant transgenes in ES cells. © 2011 Chen et al.

Published
2016

4. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

Author

Lynn Quek, Anne Goriely, Ondrej Cais, Christopher Yau, Lars Fugger, John Broxholme, Niko Popitsch, David Beeson, Zoya Kingsbury, M. Andrew Nesbit, David J. Nutt, Christopher Holmes, Andrew J. Rimmer, Fredrik Karpe, John Taylor, Andrea H. Németh, Veronica J. Buckle, Rodney D. Gilbert, Natasha Sahgal, Sian E. Piret, Alistair T. Pagnamenta, Elizabeth Sweeney, Stefano Lise, Sarah Lamble, Moustafa Attar, Christian Babbs, Mary Frances McMullin, Adrian V. S. Hill, Ingo H. Greger, Per Soelberg Sørensen, Michael P. Whyte, Paolo Piazza, Lorna Witty, Lorne Lonie, Emma E. Davenport, Peter J. Ratcliffe, Peter Humburg, Simon J. McGowan, Holger Cario, Chris Allan, Usha Kini, Malcolm F. Howard, Alexandra Russo, Simon Fiddy, Fiona Powrie, Pauline A. van Schouwenburg, Jude Craft, Andrew O.M. Wilkie, Aimee L. Fenwick, Jennifer Becq, Elizabeth Ormondroyd, Nayia Petousi, Richard R. Copley, Joshua Luck, David Buck, Hilary C. Martin, Katherine R. Bull, Holm H. Uhlig, Russell J. Grocock, Timothy J. Vyse, Smita Y. Patel, Gerton Lunter, Sean Humphray, Helen Chapel, Peter Donnelly, Karin Dahan, Calliope A. Dendrou, Edward Blair, Peter A. Robbins, Davis J. McCarthy, Kerry A. Miller, Rajesh V. Thakker, A. Radu Aricescu, Gilean McVean, Alison Simmons, Annette Bang Oturai, Julian C. Knight, David W. Johnson, Craig B. Langman, Earl D. Silverman, Anja V. Gruszczyk, Olivier Devuyst, Jean-Baptiste Cazier, Paresh Vyas, John I. Bell, Kathryn J. H. Robson, Ian Tomlinson, Jenny C. Taylor, Amy Trebes, Anna Schuh, Linda Hughes, Stephen R.F. Twigg, Hugh Watkins, Celeste Bento, Melanie J. Percy, Robert W. Hastings, Jonathan Flint, Richard J. Cornall, Edouard Hatton, Doug Higgs, P Bignell, Guadalupe Polanco-Echeverry, Angie Green, Jon P. Krohn, Ben Wright, David Bentley, Christopher W. Pugh, Steven A. Wall, Lisa Murray, and Alexander Kanapin

Subjects
HEREDITARY BREAST, Candidate gene, medicine.medical_specialty, DNA Mutational Analysis, EXOME, LONG-QT SYNDROME, Biology, Genome, Polymorphism, Single Nucleotide, Sensitivity and Specificity, DNA sequencing, Article, OVARIAN-CANCER, CANDIDATE GENES, Genetics, medicine, BREAST-CANCER, Humans, JUVENILE MYELOMONOCYTIC LEUKEMIA, Exome, Whole genome sequencing, Genetics & Heredity, SEVERE INTELLECTUAL DISABILITY, Science & Technology, Base Sequence, Genome, Human, Genetic Diseases, Inborn, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, GERMLINE MUTATIONS, 11 Medical And Health Sciences, 06 Biological Sciences, Molecular Diagnostic Techniques, Medical genetics, Human genome, Biological plausibility, DISEASE GENE-DISCOVERY, Life Sciences & Biomedicine, Developmental Biology
Abstract

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Published
2016

5. Exposure to a context previously associated with nausea elicits conditioned gaping in rats: A model of anticipatory nausea

Author

Cheryl L. Limebeer, Klaus-Peter Ossenkopp, Linda A. Parker, Shelley K. Cross-Mellor, Devin E. Litt, and Jon P. Krohn

Subjects
Male, Rotation, Lithium (medication), Side effect, Motion Sickness, medicine.drug_class, Nausea, medicine.medical_treatment, Conditioning, Classical, Context (language use), Pharmacology, Rats, Sprague-Dawley, Behavioral Neuroscience, Physical Stimulation, medicine, Animals, Chemotherapy, Behavior, Animal, Mood stabilizer, Rats, Odor, Data Interpretation, Statistical, Taste, Odorants, Vomiting, Vestibule, Labyrinth, Vomiting, Anticipatory, Cues, medicine.symptom, Lithium Chloride, Psychology, Social psychology, medicine.drug
Abstract

Following one or more chemotherapy treatments, many patients report that they experience anticipatory nausea. This phase of nausea has been interpreted as a classically conditioned response where a conditional association develops between the contextual clinic cues and the nausea and/or vomiting that developed following treatment. Although rats do not vomit, they display a distinctive gaping reaction when exposed a flavored solution previously paired with a toxin. Here we report that, even in the absence of a flavored solution, rats display conditioned gaping reactions during exposure to a distinctive context previously paired with a high dose of lithium (Experiment 1 with a distinctive odor and Experiment 3 without a distinctive odor), a low dose of lithium (Experiment 2) or provocative vestibular stimulation (Experiment 2). These results suggest that the conditioned gaping reaction in rats is selectively elicited by nausea-paired contextual stimuli, as well as flavors. This rat model of anticipatory nausea may serve as a valuable preclinical tool to evaluate the effectiveness of anti-nausea treatments and the side effect of nausea produced by newly developed pharmaceutical compounds intended for other clinical treatments.

Published
2008

6. Supplementary Material 1

Author

Henry Völzke, Tõnu Esko, Ken K. Ong, Aldi T. Kraja, Anne U. Jackson, Meena Kumari, Eva Albrecht, Rona J. Strawbridge, Antti Jula, Mark J. Caulfield, Alistair S. Hall, Karol Estrada, Jennifer L. Bolton, Teresa Ferreira, Inger Njølstad, Thomas W. Winkler, Ross M. Fraser, Daniel I. Chasman, Maris Teder-Laving, Yii-Der Ida Chen, Claudia Langenberg, Kevin B. Jacobs, Jennifer G. Sambrook, Evelin Mihailov, Peter Kovacs, Susanne Moebus, Jouke-Jan Hottenga, George Dedoussis, Gudmar Thorleifsson, Sirkka M. Keinanen Kiukaanniemi, Matti Uusitupa, Denise Anderson, Lindsay L. Waite, Johan G. Eriksson, Mustafa Atalay, Kari Stefansson, Amélie Bonnefond, Gerry Fowkes, Tove Fall, Dmitry Shungin, Stephan J. L. Bakker, Tamara B. Harris, Thomas Illig, Wolfgang Koenig, Heribert Schunkert, Caroline S. Fox, Gabrielle Boucher, Sonja I. Berndt, Timo Saaristo, Maria Dimitriou, Pim van der Harst, Christina Loley, John Yarnell, Rainer Rauramaa, Sarah Edkins, Jaakko Tuomilehto, Karen L. Mohlke, Damien C. Croteau Chonka, Reedik Mägi, Olli T. Raitakari, Kathleen Stirrups, Aroon D. Hingorani, Inga Prokopenko, Henrik Grönberg, Marcus E. Kleber, Massimo Mangino, Michael A. Province, Markus M. Nöthen, Patricia B. Munroe, Francis S. Collins, Jeanette Erdmann, Mattias Lorentzon, Lynda M. Rose, Jon P. Krohn, Paul M. Ridker, M. Carola Zillikens, Jouko Saramies, Andrew Wong, Anuj Goel, Christa Buechler, Chris Power, Iain Mathieson, Bernhard O. Boehm, Jonathan Tyrer, Fredrik Karpe, Lu Qi, Nicholas G. Martin, Kristian Hveem, Jackie F. Price, Martin Farrall, Albert V. Smith, Mary F. Feitosa, Caroline Hayward, Juha Sinisalo, Stavroula Kanoni, Elina Hyppönen, Christian Hengstenberg, Lori L. Bonnycastle, Ilja M. Nolte, Sonali Pechlivanis, Barbara Thorand, Patrik K. E. Magnusson, Cristina Barlassina, Andrew A. Hicks, Genovefa Kolovou, Melanie M. van der Klauw, Markus Perola, Tsegaselassie Workalemahu, Ida Surakka, Veikko Salomaa, Andrea Ganna, Timothy M. Frayling, Iris M. Heid, Brenda W.J.H. Penninx, Stephen J. Chanock, Jeffrey R. O'Connell, Tom Wilsgaard, Alan R. Shuldiner, David J. Hunter, Deborah J. Clegg, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, David P. Strachan, Lyle J. Palmer, Alexander Teumer, Kari E. North, L. Adrienne Cupples, Carlos Iribarren, Anna-Liisa Hartikainen, Andrew R. Wood, Lambertus A. Kiemeney, Ulf Gyllensten, Jennie Hui, Tim D. Spector, Paul W. Franks, Andrew D. Morris, Ruth J. F. Loos, George Nicholson, Felix R. Day, Kati Kristiansson, Talin Haritunians, Martina Müller-Nurasyid, Sailaja Vedantam, Pablo V. Gejman, Martin den Heijer, Andrea Maschio, Anke Tönjes, Kari Kuulasmaa, Raimund Erbel, Markku Laakso, Devin Absher, Narisu Narisu, Zhaoming Wang, Jing Hua Zhao, Thomas N. Person, Irene Mateo Leach, Mark I. McCarthy, Albert Hofman, Joel N. Hirschhorn, H.-Erich Wichmann, Nicholas J. Wareham, André Scherag, Jarmo Virtamo, James F. Wilson, Gonçalo R. Abecasis, Winfried März, Nilesh J. Samani, Timo A. Lakka, Jacques S. Beckmann, Harold Snieder, Adam E. Locke, Hanneke Basart, Grant W. Montgomery, Robert C. Kaplan, Claudia Lamina, Sekar Kathiresan, Mika Kivimäki, Leif Groop, Emil Rehnberg, Jana V. Van Vliet Ostaptchouk, Ingrid B. Borecki, Sabrina Bauer, Terho Lehtimäki, Steve E. Humphries, Zoltán Kutalik, Kees Hovingh, Carolina Medina-Gomez, Panos Deloukas, Antony P. Attwood, Kay-Tee Khaw, Per Hall, Jaakko Kaprio, Jian Yang, Tuomas O. Kilpeläinen, Andres Metspalu, Igor Rudan, Michael Boehnke, Ben A. Oostra, Jaana Lindström, André G. Uitterlinden, Peter Schwarz, Keri L. Monda, John Beilby, Fernando Rivadeneira, Emmanouil T. Dermitzakis, Dominique Arveiler, Valgerdur Steinthorsdottir, Jian'an Luan, Cecilia M. Lindgren, Guo Li, Bruna Gigante, Göran Hallmans, Liming Liang, Peter S. Chines, Sarah E. Medland, Joseph Hung, Peter P. Pramstaller, Ulf de Faire, Joshua C. Randall, Nancy L. Pedersen, Wendy L. McArdle, Unnur Thorsteinsdottir, Bernhard R. Winkelmann, Kaarel KrjutÅ¡kov, Philippe Froguel, Harry Campbell, Dorret I. Boomsma, Harald Grallert, Nancy L. Heard Costa, Shengxu Li, Amy J. Swift, Diana Kuh, Gerjan Navis, Christian Gieger, Heikki V. Huikuri, Niina Eklund, Anders Hamsten, Elizabeth K. Speliotes, Josine L. Min, Hendrik B. Sager, Stefan Gustafsson, Antigone S. Dimas, Elena Tremoli, Carlo Rivolta, Jianxin Shi, Najaf Amin, Claes Ohlsson, Johanna Kuusisto, Giancarlo Cesana, Lars Lind, Stefan R. Bornstein, Erik Ingelsson, Colin N. A. Palmer, Marjo-Riitta Järvelin, Krista Fischer, Annette Peters, David Schlessinger, Themistocles L. Assimes, Inês Barroso, Kristina Eisinger, Marja-Liisa Lokki, Jennifer Jolley, and Åsa Johansson

Subjects
Cultural Studies, Archeology, History, Chemistry, Cystolith, medicine, Magnesium ammonium phosphate, Bladder stones, medicine.disease, Nuclear chemistry
Published
2013

7. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France

Author

Blanca M. Herrera, S. Vukusic, S M Orton, C. Confavreux, A D Sadovnick, L. Wald, Jon P. Krohn, Sreeram V. Ramagopalan, George C. Ebers, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], CEP/Sophia, Centre Énergétique et Procédés (CEP), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Neuro-oncologie et neuro-inflammation, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), and Division of Neurology, University of British Columbia

Subjects
Male, medicine.medical_specialty, Ultraviolet Rays, Cross-sectional study, Population, Prevalence, Comorbidity, Environment, multiple sclerosis, UV radiation, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Epidemiology, medicine, Humans, Risk factor, SoDa, education, skin and connective tissue diseases, solar exposure, Skin, Sunlight, Sex Characteristics, education.field_of_study, integumentary system, Ecology, business.industry, Ecological study, Articles, sex ratio, Vitamin D Deficiency, Cross-Sectional Studies, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), France, business, 030217 neurology & neurosurgery, Sex ratio, Demography
Abstract

International audience; Background: French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor. Methods: Mean annual and winter (December–March) UVB irradiation values were systematically compared to MS prevalence rates in corresponding regions of France. UVB data were obtained from the solar radiation database (SoDa) service and prevalence rates from previously published data on 2,667 MS cases registered with the national farmer health insurance system, Mutualité Sociale Agricole (MSA). Pearson correlation was used to examine the relationship of annual and winter UVB values with MS prevalence. Male and female prevalence were also analyzed separately. Linear regression was used to test for interaction of annual and winter UVB with sex in predicting MS prevalence. Results: There was a strong association between MS prevalence and annual mean UVB irradiation (r = −0.80, p < 0.001) and average winter UVB (r = −0.87, p < 0.001). Both female (r = −0.76, p < 0.001) and male (r = −0.46, p = 0.032) prevalence rates were correlated with annual UVB. Regression modeling showed that the effect of UVB on prevalence rates differed by sex; the interaction effect was significant for both annual UVB (p = 0.003) and winter UVB (p = 0.002). Conclusions: The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure.

Published
2011

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