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Meta-Analysis
. 2015 Oct 1;11(10):e1005378.
doi: 10.1371/journal.pgen.1005378. eCollection 2015 Oct.

The Influence of Age and Sex on Genetic Associations With Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Thomas W Winkler  1 Anne E Justice  2 Mariaelisa Graff  2 Llilda Barata  3 Mary F Feitosa  3 Su Chu  4 Jacek Czajkowski  3 Tõnu Esko  5 Tove Fall  6 Tuomas O Kilpeläinen  7 Yingchang Lu  8 Reedik Mägi  9 Evelin Mihailov  10 Tune H Pers  11 Sina Rüeger  12 Alexander Teumer  13 Georg B Ehret  14 Teresa Ferreira  15 Nancy L Heard-Costa  16 Juha Karjalainen  17 Vasiliki Lagou  18 Anubha Mahajan  15 Michael D Neinast  19 Inga Prokopenko  20 Jeannette Simino  21 Tanya M Teslovich  4 Rick Jansen  22 Harm-Jan Westra  23 Charles C White  24 Devin Absher  25 Tarunveer S Ahluwalia  26 Shafqat Ahmad  27 Eva Albrecht  28 Alexessander Couto Alves  29 Jennifer L Bragg-Gresham  4 Anton J M de Craen  30 Joshua C Bis  31 Amélie Bonnefond  32 Gabrielle Boucher  33 Gemma Cadby  34 Yu-Ching Cheng  35 Charleston W K Chiang  36 Graciela Delgado  37 Ayse Demirkan  38 Nicole Dueker  39 Niina Eklund  40 Gudny Eiriksdottir  41 Joel Eriksson  42 Bjarke Feenstra  43 Krista Fischer  10 Francesca Frau  44 Tessel E Galesloot  45 Frank Geller  43 Anuj Goel  46 Mathias Gorski  47 Tanja B Grammer  37 Stefan Gustafsson  6 Saskia Haitjema  48 Jouke-Jan Hottenga  49 Jennifer E Huffman  50 Anne U Jackson  4 Kevin B Jacobs  51 Åsa Johansson  52 Marika Kaakinen  53 Marcus E Kleber  37 Jari Lahti  54 Irene Mateo Leach  55 Benjamin Lehne  56 Youfang Liu  57 Ken Sin Lo  33 Mattias Lorentzon  42 Jian'an Luan  58 Pamela A F Madden  59 Massimo Mangino  60 Barbara McKnight  61 Carolina Medina-Gomez  62 Keri L Monda  63 May E Montasser  64 Gabriele Müller  65 Martina Müller-Nurasyid  66 Ilja M Nolte  67 Kalliope Panoutsopoulou  68 Laura Pascoe  69 Lavinia Paternoster  70 Nigel W Rayner  71 Frida Renström  27 Federica Rizzi  44 Lynda M Rose  72 Kathy A Ryan  64 Perttu Salo  73 Serena Sanna  74 Hubert Scharnagl  75 Jianxin Shi  76 Albert Vernon Smith  77 Lorraine Southam  78 Alena Stančáková  79 Valgerdur Steinthorsdottir  80 Rona J Strawbridge  81 Yun Ju Sung  21 Ioanna Tachmazidou  68 Toshiko Tanaka  82 Gudmar Thorleifsson  80 Stella Trompet  83 Natalia Pervjakova  84 Jonathan P Tyrer  85 Liesbeth Vandenput  42 Sander W van der Laan  48 Nathalie van der Velde  86 Jessica van Setten  87 Jana V van Vliet-Ostaptchouk  88 Niek Verweij  55 Efthymia Vlachopoulou  89 Lindsay L Waite  25 Sophie R Wang  90 Zhaoming Wang  51 Sarah H Wild  91 Christina Willenborg  92 James F Wilson  93 Andrew Wong  94 Jian Yang  95 Loïc Yengo  32 Laura M Yerges-Armstrong  64 Lei Yu  96 Weihua Zhang  97 Jing Hua Zhao  58 Ehm A Andersson  98 Stephan J L Bakker  99 Damiano Baldassarre  100 Karina Banasik  98 Matteo Barcella  101 Cristina Barlassina  101 Claire Bellis  102 Paola Benaglio  103 John Blangero  104 Matthias Blüher  105 Fabrice Bonnet  106 Lori L Bonnycastle  107 Heather A Boyd  43 Marcel Bruinenberg  108 Aron S Buchman  96 Harry Campbell  93 Yii-Der Ida Chen  109 Peter S Chines  107 Simone Claudi-Boehm  110 John Cole  111 Francis S Collins  107 Eco J C de Geus  112 Lisette C P G M de Groot  113 Maria Dimitriou  114 Jubao Duan  115 Stefan Enroth  52 Elodie Eury  32 Aliki-Eleni Farmaki  116 Nita G Forouhi  58 Nele Friedrich  117 Pablo V Gejman  115 Bruna Gigante  118 Nicola Glorioso  119 Alan S Go  120 Omri Gottesman  121 Jürgen Gräßler  122 Harald Grallert  123 Niels Grarup  98 Yu-Mei Gu  124 Linda Broer  125 Annelies C Ham  125 Torben Hansen  126 Tamara B Harris  127 Catharina A Hartman  128 Maija Hassinen  129 Nicholas Hastie  130 Andrew T Hattersley  131 Andrew C Heath  59 Anjali K Henders  132 Dena Hernandez  133 Hans Hillege  55 Oddgeir Holmen  134 Kees G Hovingh  135 Jennie Hui  136 Lise L Husemoen  137 Nina Hutri-Kähönen  138 Pirro G Hysi  60 Thomas Illig  139 Philip L De Jager  140 Shapour Jalilzadeh  46 Torben Jørgensen  141 J Wouter Jukema  142 Markus Juonala  143 Stavroula Kanoni  144 Maria Karaleftheri  145 Kay Tee Khaw  146 Leena Kinnunen  147 Steven J Kittner  111 Wolfgang Koenig  148 Ivana Kolcic  149 Peter Kovacs  150 Nikolaj T Krarup  98 Wolfgang Kratzer  110 Janine Krüger  151 Diana Kuh  94 Meena Kumari  152 Theodosios Kyriakou  46 Claudia Langenberg  153 Lars Lannfelt  154 Chiara Lanzani  155 Vaneet Lotay  156 Lenore J Launer  157 Karin Leander  118 Jaana Lindström  158 Allan Linneberg  159 Yan-Ping Liu  124 Stéphane Lobbens  32 Robert Luben  160 Valeriya Lyssenko  161 Satu Männistö  162 Patrik K Magnusson  163 Wendy L McArdle  164 Cristina Menni  60 Sigrun Merger  110 Lili Milani  10 Grant W Montgomery  132 Andrew P Morris  165 Narisu Narisu  107 Mari Nelis  10 Ken K Ong  166 Aarno Palotie  167 Louis Pérusse  168 Irene Pichler  169 Maria G Pilia  74 Anneli Pouta  170 Myriam Rheinberger  171 Rasmus Ribel-Madsen  98 Marcus Richards  94 Kenneth M Rice  172 Treva K Rice  173 Carlo Rivolta  174 Veikko Salomaa  162 Alan R Sanders  115 Mark A Sarzynski  175 Salome Scholtens  67 Robert A Scott  58 William R Scott  97 Sylvain Sebert  176 Sebanti Sengupta  4 Bengt Sennblad  177 Thomas Seufferlein  110 Angela Silveira  81 P Eline Slagboom  178 Jan H Smit  22 Thomas H Sparsø  98 Kathleen Stirrups  144 Ronald P Stolk  67 Heather M Stringham  4 Morris A Swertz  17 Amy J Swift  107 Ann-Christine Syvänen  179 Sian-Tsung Tan  180 Barbara Thorand  181 Anke Tönjes  182 Angelo Tremblay  183 Emmanouil Tsafantakis  184 Peter J van der Most  67 Uwe Völker  185 Marie-Claude Vohl  186 Judith M Vonk  67 Melanie Waldenberger  187 Ryan W Walker  8 Roman Wennauer  188 Elisabeth Widén  189 Gonneke Willemsen  49 Tom Wilsgaard  190 Alan F Wright  130 M Carola Zillikens  191 Suzanne C van Dijk  125 Natasja M van Schoor  192 Folkert W Asselbergs  193 Paul I W de Bakker  194 Jacques S Beckmann  195 John Beilby  196 David A Bennett  96 Richard N Bergman  197 Sven Bergmann  198 Carsten A Böger  171 Bernhard O Boehm  199 Eric Boerwinkle  200 Dorret I Boomsma  49 Stefan R Bornstein  201 Erwin P Bottinger  121 Claude Bouchard  175 John C Chambers  202 Stephen J Chanock  203 Daniel I Chasman  204 Francesco Cucca  205 Daniele Cusi  206 George Dedoussis  116 Jeanette Erdmann  92 Johan G Eriksson  207 Denis A Evans  208 Ulf de Faire  118 Martin Farrall  209 Luigi Ferrucci  82 Ian Ford  210 Lude Franke  211 Paul W Franks  212 Philippe Froguel  32 Ron T Gansevoort  99 Christian Gieger  213 Henrik Grönberg  163 Vilmundur Gudnason  77 Ulf Gyllensten  52 Per Hall  163 Anders Hamsten  214 Pim van der Harst  215 Caroline Hayward  130 Markku Heliövaara  147 Christian Hengstenberg  216 Andrew A Hicks  169 Aroon Hingorani  217 Albert Hofman  218 Frank Hu  219 Heikki V Huikuri  220 Kristian Hveem  134 Alan L James  221 Joanne M Jordan  57 Antti Jula  162 Mika Kähönen  222 Eero Kajantie  223 Sekar Kathiresan  224 Lambertus A L M Kiemeney  225 Mika Kivimaki  152 Paul B Knekt  226 Heikki A Koistinen  227 Jaspal S Kooner  228 Seppo Koskinen  147 Johanna Kuusisto  79 Winfried Maerz  229 Nicholas G Martin  132 Markku Laakso  79 Timo A Lakka  230 Terho Lehtimäki  231 Guillaume Lettre  232 Douglas F Levinson  233 Lars Lind  234 Marja-Liisa Lokki  89 Pekka Mäntyselkä  235 Mads Melbye  236 Andres Metspalu  10 Braxton D Mitchell  237 Frans L Moll  238 Jeffrey C Murray  239 Arthur W Musk  240 Markku S Nieminen  241 Inger Njølstad  190 Claes Ohlsson  42 Albertine J Oldehinkel  242 Ben A Oostra  38 Lyle J Palmer  243 James S Pankow  244 Gerard Pasterkamp  48 Nancy L Pedersen  163 Oluf Pedersen  98 Brenda W Penninx  22 Markus Perola  245 Annette Peters  187 Ozren Polašek  246 Peter P Pramstaller  247 Bruce M Psaty  248 Lu Qi  219 Thomas Quertermous  249 Olli T Raitakari  250 Tuomo Rankinen  175 Rainer Rauramaa  251 Paul M Ridker  204 John D Rioux  232 Fernando Rivadeneira  62 Jerome I Rotter  109 Igor Rudan  93 Hester M den Ruijter  48 Juha Saltevo  252 Naveed Sattar  253 Heribert Schunkert  216 Peter E H Schwarz  201 Alan R Shuldiner  254 Juha Sinisalo  241 Harold Snieder  67 Thorkild I A Sørensen  255 Tim D Spector  60 Jan A Staessen  256 Bandinelli Stefania  257 Unnur Thorsteinsdottir  258 Michael Stumvoll  105 Jean-Claude Tardif  232 Elena Tremoli  100 Jaakko Tuomilehto  259 André G Uitterlinden  62 Matti Uusitupa  260 André L M Verbeek  45 Sita H Vermeulen  261 Jorma S Viikari  262 Veronique Vitart  130 Henry Völzke  263 Peter Vollenweider  264 Gérard Waeber  264 Mark Walker  265 Henri Wallaschofski  266 Nicholas J Wareham  58 Hugh Watkins  46 Eleftheria Zeggini  68 CHARGE ConsortiumDIAGRAM ConsortiumGLGC ConsortiumGlobal-BPGen ConsortiumICBP ConsortiumMAGIC ConsortiumAravinda Chakravarti  267 Deborah J Clegg  19 L Adrienne Cupples  268 Penny Gordon-Larsen  269 Cashell E Jaquish  270 D C Rao  271 Goncalo R Abecasis  4 Themistocles L Assimes  249 Inês Barroso  272 Sonja I Berndt  273 Michael Boehnke  4 Panos Deloukas  274 Caroline S Fox  275 Leif C Groop  276 David J Hunter  277 Erik Ingelsson  278 Robert C Kaplan  279 Mark I McCarthy  280 Karen L Mohlke  281 Jeffrey R O'Connell  64 David Schlessinger  157 David P Strachan  282 Kari Stefansson  258 Cornelia M van Duijn  283 Joel N Hirschhorn  284 Cecilia M Lindgren  285 Iris M 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Free PMC article
Meta-Analysis

The Influence of Age and Sex on Genetic Associations With Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Thomas W Winkler et al. PLoS Genet. .
Free PMC article

Erratum in

  • Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
    Winkler TW, Justice AE, Graff M, Barata L, Feitosa MF, Chu S, Czajkowski J, Esko T, Fall T, Kilpeläinen TO, Lu Y, Mägi R, Mihailov E, Pers TH, Rüeger S, Teumer A, Ehret GB, Ferreira T, Heard-Costa NL, Karjalainen J, Lagou V, Mahajan A, Neinast MD, Prokopenko I, Simino J, Teslovich TM, Jansen R, Westra HJ, White CC, Absher D, Ahluwalia TS, Ahmad S, Albrecht E, Alves AC, Bragg-Gresham JL, de Craen AJ, Bis JC, Bonnefond A, Boucher G, Cadby G, Cheng YC, Chiang CW, Delgado G, Demirkan A, Dueker N, Eklund N, Eiriksdottir G, Eriksson J, Feenstra B, Fischer K, Frau F, Galesloot TE, Geller F, Goel A, Gorski M, Grammer TB, Gustafsson S, Haitjema S, Hottenga JJ, Huffman JE, Jackson AU, Jacobs KB, Johansson Å, Kaakinen M, Kleber ME, Lahti J, Mateo Leach I, Lehne B, Liu Y, Lo KS, Lorentzon M, Luan J, Madden PA, Mangino M, McKnight B, Medina-Gomez C, Monda KL, Montasser ME, Müller G, Müller-Nurasyid M, Nolte IM, Panoutsopoulou K, Pascoe L, Paternoster L, Rayner NW, Renström F, Rizzi F, Rose LM, Ryan KA, Salo P, Sanna S, Scharnagl H, Shi J, Smith AV, Southam L, Stančáková A, Steinthorsdottir V, Strawbridge RJ, Sung YJ, Tachmazidou I, Tanaka T, Thorleifsson G, Trompet S, Pervjakova N, Tyrer JP, Vandenput L, van der Laan SW, van der Velde N, van Setten J, van Vliet-Ostaptchouk JV, Verweij N, Vlachopoulou E, Waite LL, Wang SR, Wang Z, Wild SH, Willenborg C, Wilson JF, Wong A, Yang J, Yengo L, Yerges-Armstrong LM, Yu L, Zhang W, Zhao JH, Andersson EA, Bakker SJ, Baldassarre D, Banasik K, Barcella M, Barlassina C, Bellis C, Benaglio P, Blangero J, Blüher M, Bonnet F, Bonnycastle LL, Boyd HA, Bruinenberg M, Buchman AS, Campbell H, Chen YI, Chines PS, Claudi-Boehm S, Cole J, Collins FS, de Geus EJ, de Groot LC, Dimitriou M, Duan J, Enroth S, Eury E, Farmaki AE, Forouhi NG, Friedrich N, Gejman PV, Gigante B, Glorioso N, Go AS, Gottesman O, Gräßler J, Grallert H, Grarup N, Gu YM, Broer L, Ham AC, Hansen T, Harris TB, Hartman CA, Hassinen M, Hastie N, Hattersley AT, Heath AC, Henders AK, Hernandez D, Hillege H, Holmen O, Hovingh KG, Hui J, Husemoen LL, Hutri-Kähönen N, Hysi PG, Illig T, De Jager PL, Jalilzadeh S, Jørgensen T, Jukema JW, Juonala M, Kanoni S, Karaleftheri M, Khaw KT, Kinnunen L, Kittner SJ, Koenig W, Kolcic I, Kovacs P, Krarup NT, Kratzer W, Krüger J, Kuh D, Kumari M, Kyriakou T, Langenberg C, Lannfelt L, Lanzani C, Lotay V, Launer LJ, Leander K, Lindström J, Linneberg A, Liu YP, Lobbens S, Luben R, Lyssenko V, Männistö S, Magnusson PK, McArdle WL, Menni C, Merger S, Milani L, Montgomery GW, Morris AP, Narisu N, Nelis M, Ong KK, Palotie A, Pérusse L, Pichler I, Pilia MG, Pouta A, Rheinberger M, Ribel-Madsen R, Richards M, Rice KM, Rice TK, Rivolta C, Salomaa V, Sanders AR, Sarzynski MA, Scholtens S, Scott RA, Scott WR, Sebert S, Sengupta S, Sennblad B, Seufferlein T, Silveira A, Slagboom PE, Smit JH, Sparsø TH, Stirrups K, Stolk RP, Stringham HM, Swertz MA, Swift AJ, Syvänen AC, Tan ST, Thorand B, Tönjes A, Tremblay A, Tsafantakis E, van der Most PJ, Völker U, Vohl MC, Vonk JM, Waldenberger M, Walker RW, Wennauer R, Widén E, Willemsen G, Wilsgaard T, Wright AF, Zillikens MC, van Dijk SC, van Schoor NM, Asselbergs FW, de Bakker PI, Beckmann JS, Beilby J, Bennett DA, Bergman RN, Bergmann S, Böger CA, Boehm BO, Boerwinkle E, Boomsma DI, Bornstein SR, Bottinger EP, Bouchard C, Chambers JC, Chanock SJ, Chasman DI, Cucca F, Cusi D, Dedoussis G, Erdmann J, Eriksson JG, Evans DA, de Faire U, Farrall M, Ferrucci L, Ford I, Franke L, Franks PW, Froguel P, Gansevoort RT, Gieger C, Grönberg H, Gudnason V, Gyllensten U, Hall P, Hamsten A, van der Harst P, Hayward C, Heliövaara M, Hengstenberg C, Hicks AA, Hingorani A, Hofman A, Hu F, Huikuri HV, Hveem K, James AL, Jordan JM, Jula A, Kähönen M, Kajantie E, Kathiresan S, Kiemeney LA, Kivimaki M, Knekt PB, Koistinen HA, Kooner JS, Koskinen S, Kuusisto J, Maerz W, Martin NG, Laakso M, Lakka TA, Lehtimäki T, Lettre G, Levinson DF, Lind L, Lokki ML, Mäntyselkä P, Melbye M, Metspalu A, Mitchell BD, Moll FL, Murray JC, Musk AW, Nieminen MS, Njølstad I, Ohlsson C, Oldehinkel AJ, Oostra BA, Palmer LJ, Pankow JS, Pasterkamp G, Pedersen NL, Pedersen O, Penninx BW, Perola M, Peters A, Polašek O, Pramstaller PP, Psaty BM, Qi L, Quertermous T, Raitakari OT, Rankinen T, Rauramaa R, Ridker PM, Rioux JD, Rivadeneira F, Rotter JI, Rudan I, den Ruijter HM, Saltevo J, Sattar N, Schunkert H, Schwarz PE, Shuldiner AR, Sinisalo J, Snieder H, Sørensen TI, Spector TD, Staessen JA, Stefania B, Thorsteinsdottir U, Stumvoll M, Tardif JC, Tremoli E, Tuomilehto J, Uitterlinden AG, Uusitupa M, Verbeek AL, Vermeulen SH, Viikari JS, Vitart V, Völzke H, Vollenweider P, Waeber G, Walker M, Wallaschofski H, Wareham NJ, Watkins H, Zeggini E; arcOGEN Consortium; CHARGE Consortium; DIAGRAM Consortium; GLGC Consortium; Global-BPGen Consortium; ICBP Consortium; MAGIC Consortium, Chakravarti A, Clegg DJ, Cupples LA, Gordon-Larsen P, Jaquish CE, Rao DC, Abecasis GR, Assimes TL, Barroso I, Berndt SI, Boehnke M, Deloukas P, Fox CS, Groop LC, Hunter DJ, Ingelsson E, Kaplan RC, McCarthy MI, Mohlke KL, O'Connell JR, Schlessinger D, Strachan DP, Stefansson K, van Duijn CM, Hirschhorn JN, Lindgren CM, Heid IM, North KE, Borecki IB, Kutalik Z, Loos RJ. Winkler TW, et al. PLoS Genet. 2016 Jun 29;12(6):e1006166. doi: 10.1371/journal.pgen.1006166. eCollection 2016 Jun. PLoS Genet. 2016. PMID: 27355579 Free PMC article.

Abstract

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Conflict of interest statement

I have read the journals policy and we have the following conflicts: KSte, UT, VSte and GT are employed by deCODE Genetics/Amgen inc. IB and spouse own stock in Incyte Ltd and GlaxoSmithKline. JMJ serves as consultant for Trinity Partners, Inc., Samumed, Flexion, and is deputy editor for Osteoarthritis & Cartilage and serves on board of directors of American College of Rheumatology. PV and GWa received an unresticted grant from GlaxoSmithKline to build the CoLaus study. BMP serves on the data and safety monitoring board (DSMB) for a clinical trial of a device funded by the manufacturer (Zoll LifeCor) and serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson.

Figures

Fig 1
Fig 1. Interaction QQ plots.
Quantile-Quantile plots showing P-Values for age-difference (P agediff, green), sex-difference (P sexdiff, blue) and age- and sex-difference (P agesexdiff, purple). For BMI the P-Values are depicted for all SNPs genome-wide (A) as well as for a limited subset of SNPs that survived pre-filtering on the overall association with BMI, P Overall < 1x10-5 (B). For WHRadjBMI the P-Values are depicted for all SNPs genome-wide (C) as well as for a limited subset of SNPs that survived pre-filtering on the overall association with WHRadjBMI, P Overall < 1x10-5 (D).
Fig 2
Fig 2. Age-dependent BMI loci.
Effect estimates (beta ±95CI) per standard deviation in BMI and risk allele for loci showing age-differences in men & women ≤50y compared to men & women >50y. Loci are ordered by greater magnitude of effect in men & women ≤50y compared to men & women >50y. (95%CI: 95% confidence interval; BMI: body mass index; SD: standard deviation, *Newly identified loci).
Fig 3
Fig 3. Sex-dependent WHRadjBMI loci.
Effect estimates (beta ± 95CI) per standard deviation in WHRadjBMI and risk allele for loci showing sex-differences in women compared to men. Loci are ordered by greater magnitude of effect in women compared to men. (95%CI: 95% confidence interval; SD: standard deviation. *Newly identified loci. † Newly identified sex-differences)
Fig 4
Fig 4. Power heatplots.
Power for the combination of screens and gain through a priori filtering for varying configurations of effect sizes across the 4 strata. The figures illustrate (A) the power to detect age-difference, sex-difference or age-sex-difference in at least one of our scans (on P agediff, P sexdiff and P agesexdiff, with and without a priori filtering); and (B) a power comparison, comparing approaches with and without a priori filtering on P Overall < 1x10-5. We here assume four equally sized strata and a total sample size of N = 300,000 (comparable to the sample size in our BMI analyses). We set bF≤50y = 0.033 (corresponding to a known and mean BMI effect in MAP2K5 region with R2 = 0.037%), bM>50y = 0, and vary bF>50y and bM≤50 on the axes. This strategy allows us to cover the most interesting and plausible interaction effects: Two-way interactions, such as (i) pure age-difference (b≤50y = 0.033, b>50y = 0) and (ii) pure sex-difference (bF = 0.033, bM = 0); and three-way interactions, such as (iii) extreme three-way interaction with opposite direction across AGE and SEX, (iv) 1-strata interaction (bF≤50y = 0.033, bF>50y = bM≤50y = bM>50y = 0), and (v) 3-strata interaction (bF≤50y = bF>50y = bM≤50y = 0.033, bM>50y = 0).

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References

    1. Vazquez G., et al. , Comparison of body mass index, waist circumference, and waist/hip ratio in predicting incident diabetes: a meta-analysis. Epidemiol Rev, 2007. 29: p. 115–28. - PubMed
    1. Pischon T., et al. , General and abdominal adiposity and risk of death in Europe. N Engl J Med, 2008. 359(20): p. 2105–20. 10.1056/NEJMoa0801891 - DOI - PubMed
    1. Mokdad A.H., et al. , Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA, 2003. 289(1): p. 76–9. - PubMed
    1. Must A., et al. , The disease burden associated with overweight and obesity. JAMA, 1999. 282(16): p. 1523–9. - PubMed
    1. Yusuf S., et al. , Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet, 2005. 366(9497): p. 1640–9. - PubMed

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