Dataset Information

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

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<5%), 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 genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

SUBMITTER: Randall JC

PROVIDER: S-EPMC3674993 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

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

PLoS genetics 20130606 6

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<5%), including four previously esta ...[more]

PMID: 23754948

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Project description:Assessing the long-term macroevolutionary consequences of sexual selection has been hampered by the difficulty of studying this process in the fossil record. Cytheroid ostracodes offer an excellent system to explore sexual selection in the fossil record because their readily fossilized carapaces are sexually dimorphic. Specifically, males are relatively more elongate than females in this superfamily. This sexual shape difference is thought to arise so that males carapaces can accommodate their very large copulatory apparatus, which can account for up to one-third of body volume. Here we test this widely held explanation for sexual dimorphism in cytheroid ostracodes by correlating investment in male genitalia, a trait in which sexual selection is seen as the main evolutionary driver, with sexual dimorphism of carapace in the genus Cyprideis. We analyzed specimens collected in the field (C. salebrosa, USA; C. torosa, UK) and from collections of the National Museum of Natural History, Washington, DC (C. mexicana). We digitized valve outlines in lateral view to obtain measures of size (valve area) and shape (elongation, measured as length to height ratio), and obtained several dimensions from two components of the hemipenis: the muscular basal capsule, which functions as a sperm pump, and the section that includes the intromittent organ (terminal extension). In addition to the assessment of this primary sexual trait, we also quantified two dimensions of the male secondary sexual trait-where the transformed right walking leg functions as a clasping organ during mating. We also measured linear dimensions from four limbs as indicators of overall (soft-part) body size, and assessed allometry of the soft anatomy. We observed significant correlations in males between valve size, but not elongation, and distinct structural parts of the hemipenis, even after accounting for their shared correlation with overall body size. We also found weak but significant positive correlation between valve elongation and the degree of sexual dimorphism of the walking leg, but only in C. torosa. The correlation between the hemipenis parts, especially basal capsule size and male valve size dimorphism suggests that sexual selection on sperm size, quantity, and/or efficiency of transfer may drive sexual size dimorphism in these species, although we cannot exclude other aspects of sexual and natural selection.

Dataset Information

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

Publications

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

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