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- Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa (2017)
- Laura M. Huckins Konstantinos Hatzikotoulas Lorraine Southam Laura M. Thornton Julia Steinberg Fernando Riveros Mckay Aguilera Janet Treasure Ulrike Schmidt Cerisse Gunasinghe Anibal Romero Charles Curtis Daniel Rhodes Julie Moens Gursharan Kalsi David Dempster Rufina Leung Aoife Keohane Roland Burghardt Stefan Ehrlich Johannes Hebebrand Anke Hinney Anja Ludolph Esther Walton Panos Deloukas Albert Hofman Aarno Palotie Priit Palta Frank J. A. van Rooij Kathleen Stirrups Roger Adan Claudette Boni Roger Cone George Dedoussis Eric van Furth Fragiskos Gonidakis Philip Gorwood James I. Hudson Jaakko Kaprio Martien Kas Anna Keski-Rahkonen Kirsty Kiezebrink Gun Peggy Knudsen Margarita C. T. Slof-Op ‘t Landt Mario Maj Alessio Maria Monteleone Palmiero Monteleone Anu Raevuori Ted Reichborn-Kjennerud Federica Tozzi Artemis Tsitsika Annemarie van Elburg David A. Collier Patrick F. Sullivan Gerome Breen Cynthia M. Bulik Eleftheria Zeggini
- Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.
- Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits (2013)
- 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 André 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 Amélie Bonnefond Philippe Froguel 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 Heinz Erich Wichmann Eva Albrecht Christian Gieger Andrew A. Hicks Åsa 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 Adrianus 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 Gordon 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 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 Maria 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. Böhm 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 Kari E. North Cecilia M. Lindgren Lu Qi Ruth J. F. Loos Iris M. Heid Joel N. Hirschhorn Mark I. McCarthy Gonçalo R. Abecasis Kari Stefansson David P. Strachan David Schlessinger Jeffrey R. O'Connell Cornelia M. van Duijn
- Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
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