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2. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
- Author
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Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L, Winkler TW, Chu AY, Mahajan A, Hadley D, Xue L, Workalemahu T, Heard-Costa NL, den Hoed M, Ahluwalia TS, Qi Q, Ngwa JS, Renström F, Quaye L, Eicher JD, Hayes JE, Cornelis M, Kutalik Z, Lim E, Luan J, Huffman JE, Zhang W, Zhao W, Griffin PJ, Haller T, Ahmad S, Marques-Vidal PM, Bien S, Yengo L, Teumer A, Smith AV, Kumari M, Harder MN, Justesen JM, Kleber ME, Hollensted M, Lohman K, Rivera NV, Whitfield JB, Zhao JH, Stringham HM, Lyytikäinen LP, Huppertz C, Willemsen G, Peyrot WJ, Wu Y, Kristiansson K, Demirkan A, Fornage M, Hassinen M, Bielak LF, Cadby G, Tanaka T, Mägi R, van der Most PJ, Jackson AU, Bragg-Gresham JL, Vitart V, Marten J, Navarro P, Bellis C, Pasko D, Johansson Å, Snitker S, Cheng YC, Eriksson J, Lim U, Aadahl M, Adair LS, Amin N, Balkau B, Auvinen J, Beilby J, Bergman RN, Bergmann S, Bertoni AG, Blangero J, Bonnefond A, Bonnycastle LL, Borja JB, Brage S, Busonero F, Buyske S, Campbell H, Chines PS, Collins FS, Corre T, Smith GD, Delgado GE, Dueker N, Dörr M, Ebeling T, Eiriksdottir G, Esko T, Faul JD, Fu M, Færch K, Gieger C, Gläser S, Gong J, Gordon-Larsen P, Grallert H, Grammer TB, Grarup N, van Grootheest G, Harald K, Hastie ND, Havulinna AS, Hernandez D, Hindorff L, Hocking LJ, Holmens OL, Holzapfel C, Hottenga JJ, Huang J, Huang T, Hui J, Huth C, Hutri-Kähönen N, James AL, Jansson JO, Jhun MA, Juonala M, Kinnunen L, Koistinen HA, Kolcic I, Komulainen P, Kuusisto J, Kvaløy K, Kähönen M, Lakka TA, Launer LJ, Lehne B, Lindgren CM, Lorentzon M, Luben R, Marre M, Milaneschi Y, Monda KL, Montgomery GW, De Moor MHM, Mulas A, Müller-Nurasyid M, Musk AW, Männikkö R, Männistö S, Narisu N, Nauck M, Nettleton JA, Nolte IM, Oldehinkel AJ, Olden M, Ong KK, Padmanabhan S, Paternoster L, Perez J, Perola M, Peters A, Peters U, Peyser PA, Prokopenko I, Puolijoki H, Raitakari OT, Rankinen T, Rasmussen-Torvik LJ, Rawal R, Ridker PM, Rose LM, Rudan I, Sarti C, Sarzynski MA, Savonen K, Scott WR, Sanna S, Shuldiner AR, Sidney S, Silbernagel G, Smith BH, Smith JA, Snieder H, Stančáková A, Sternfeld B, Swift AJ, Tammelin T, Tan ST, Thorand B, Thuillier D, Vandenput L, Vestergaard H, van Vliet-Ostaptchouk JV, Vohl MC, Völker U, Waeber G, Walker M, Wild S, Wong A, Wright AF, Zillikens MC, Zubair N, Haiman CA, Lemarchand L, Gyllensten U, Ohlsson C, Hofman A, Rivadeneira F, Uitterlinden AG, Pérusse L, Wilson JF, Hayward C, Polasek O, Cucca F, Hveem K, Hartman CA, Tönjes A, Bandinelli S, Palmer LJ, Kardia SLR, Rauramaa R, Sørensen TIA, Tuomilehto J, Salomaa V, Penninx BWJH, de Geus EJC, Boomsma DI, Lehtimäki T, Mangino M, Laakso M, Bouchard C, Martin NG, Kuh D, Liu Y, Linneberg A, März W, Strauch K, Kivimäki M, Harris TB, Gudnason V, Völzke H, Qi L, Järvelin MR, Chambers JC, Kooner JS, Froguel P, Kooperberg C, Vollenweider P, Hallmans G, Hansen T, Pedersen O, Metspalu A, Wareham NJ, Langenberg C, Weir DR, Porteous DJ, Boerwinkle E, Chasman DI, Abecasis GR, Barroso I, McCarthy MI, Frayling TM, O'Connell JR, van Duijn CM, Boehnke M, Heid IM, Mohlke KL, Strachan DP, Fox CS, Liu CT, Hirschhorn JN, Klein RJ, Johnson AD, Borecki IB, Franks PW, North KE, Cupples LA, Loos RJF, and Kilpeläinen TO
- Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1006528.].
- Published
- 2017
- Full Text
- View/download PDF
3. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
- Author
-
Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L, Winkler TW, Chu AY, Mahajan A, Hadley D, Xue L, Workalemahu T, Heard-Costa NL, den Hoed M, Ahluwalia TS, Qi Q, Ngwa JS, Renström F, Quaye L, Eicher JD, Hayes JE, Cornelis M, Kutalik Z, Lim E, Luan J, Huffman JE, Zhang W, Zhao W, Griffin PJ, Haller T, Ahmad S, Marques-Vidal PM, Bien S, Yengo L, Teumer A, Smith AV, Kumari M, Harder MN, Justesen JM, Kleber ME, Hollensted M, Lohman K, Rivera NV, Whitfield JB, Zhao JH, Stringham HM, Lyytikäinen LP, Huppertz C, Willemsen G, Peyrot WJ, Wu Y, Kristiansson K, Demirkan A, Fornage M, Hassinen M, Bielak LF, Cadby G, Tanaka T, Mägi R, van der Most PJ, Jackson AU, Bragg-Gresham JL, Vitart V, Marten J, Navarro P, Bellis C, Pasko D, Johansson Å, Snitker S, Cheng YC, Eriksson J, Lim U, Aadahl M, Adair LS, Amin N, Balkau B, Auvinen J, Beilby J, Bergman RN, Bergmann S, Bertoni AG, Blangero J, Bonnefond A, Bonnycastle LL, Borja JB, Brage S, Busonero F, Buyske S, Campbell H, Chines PS, Collins FS, Corre T, Smith GD, Delgado GE, Dueker N, Dörr M, Ebeling T, Eiriksdottir G, Esko T, Faul JD, Fu M, Færch K, Gieger C, Gläser S, Gong J, Gordon-Larsen P, Grallert H, Grammer TB, Grarup N, van Grootheest G, Harald K, Hastie ND, Havulinna AS, Hernandez D, Hindorff L, Hocking LJ, Holmens OL, Holzapfel C, Hottenga JJ, Huang J, Huang T, Hui J, Huth C, Hutri-Kähönen N, James AL, Jansson JO, Jhun MA, Juonala M, Kinnunen L, Koistinen HA, Kolcic I, Komulainen P, Kuusisto J, Kvaløy K, Kähönen M, Lakka TA, Launer LJ, Lehne B, Lindgren CM, Lorentzon M, Luben R, Marre M, Milaneschi Y, Monda KL, Montgomery GW, De Moor MHM, Mulas A, Müller-Nurasyid M, Musk AW, Männikkö R, Männistö S, Narisu N, Nauck M, Nettleton JA, Nolte IM, Oldehinkel AJ, Olden M, Ong KK, Padmanabhan S, Paternoster L, Perez J, Perola M, Peters A, Peters U, Peyser PA, Prokopenko I, Puolijoki H, Raitakari OT, Rankinen T, Rasmussen-Torvik LJ, Rawal R, Ridker PM, Rose LM, Rudan I, Sarti C, Sarzynski MA, Savonen K, Scott WR, Sanna S, Shuldiner AR, Sidney S, Silbernagel G, Smith BH, Smith JA, Snieder H, Stančáková A, Sternfeld B, Swift AJ, Tammelin T, Tan ST, Thorand B, Thuillier D, Vandenput L, Vestergaard H, van Vliet-Ostaptchouk JV, Vohl MC, Völker U, Waeber G, Walker M, Wild S, Wong A, Wright AF, Zillikens MC, Zubair N, Haiman CA, Lemarchand L, Gyllensten U, Ohlsson C, Hofman A, Rivadeneira F, Uitterlinden AG, Pérusse L, Wilson JF, Hayward C, Polasek O, Cucca F, Hveem K, Hartman CA, Tönjes A, Bandinelli S, Palmer LJ, Kardia SLR, Rauramaa R, Sørensen TIA, Tuomilehto J, Salomaa V, Penninx BWJH, de Geus EJC, Boomsma DI, Lehtimäki T, Mangino M, Laakso M, Bouchard C, Martin NG, Kuh D, Liu Y, Linneberg A, März W, Strauch K, Kivimäki M, Harris TB, Gudnason V, Völzke H, Qi L, Järvelin MR, Chambers JC, Kooner JS, Froguel P, Kooperberg C, Vollenweider P, Hallmans G, Hansen T, Pedersen O, Metspalu A, Wareham NJ, Langenberg C, Weir DR, Porteous DJ, Boerwinkle E, Chasman DI, Abecasis GR, Barroso I, McCarthy MI, Frayling TM, O'Connell JR, van Duijn CM, Boehnke M, Heid IM, Mohlke KL, Strachan DP, Fox CS, Liu CT, Hirschhorn JN, Klein RJ, Johnson AD, Borecki IB, Franks PW, North KE, Cupples LA, Loos RJF, and Kilpeläinen TO
- Subjects
- Adiposity physiology, Body Mass Index, Epigenomics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Obesity physiopathology, Waist Circumference, Waist-Hip Ratio, Adiposity genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Exercise, Obesity genetics
- Abstract
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
- Published
- 2017
- Full Text
- View/download PDF
4. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
- Author
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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, 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, and Loos RJ
- Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1005378.].
- Published
- 2016
- Full Text
- View/download PDF
5. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
- Author
-
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 YD, 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, 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, and Loos RJ
- Subjects
- Adult, Age Factors, Aged, Chromosome Mapping, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Sex Characteristics, Waist-Hip Ratio, White People, Body Mass Index, Body Size genetics, Genetic Predisposition to Disease, Genome-Wide Association Study
- 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.
- Published
- 2015
- Full Text
- View/download PDF
6. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
- Author
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Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, Monda KL, Kilpeläinen TO, Esko T, Mägi R, Li S, Workalemahu T, Feitosa MF, Croteau-Chonka DC, Day FR, Fall T, Ferreira T, Gustafsson S, Locke AE, Mathieson I, Scherag A, Vedantam S, Wood AR, Liang L, Steinthorsdottir V, Thorleifsson G, Dermitzakis ET, Dimas AS, Karpe F, Min JL, Nicholson G, Clegg DJ, Person T, Krohn JP, Bauer S, Buechler C, Eisinger K, Bonnefond A, Froguel P, Hottenga JJ, Prokopenko I, Waite LL, Harris TB, Smith AV, Shuldiner AR, McArdle WL, Caulfield MJ, Munroe PB, Grönberg H, Chen YD, Li G, Beckmann JS, Johnson T, Thorsteinsdottir U, Teder-Laving M, Khaw KT, Wareham NJ, Zhao JH, Amin N, Oostra BA, Kraja AT, Province MA, Cupples LA, Heard-Costa NL, Kaprio J, Ripatti S, Surakka I, Collins FS, Saramies J, Tuomilehto J, Jula A, Salomaa V, Erdmann J, Hengstenberg C, Loley C, Schunkert H, Lamina C, Wichmann HE, Albrecht E, Gieger C, Hicks AA, Johansson A, Pramstaller PP, Kathiresan S, Speliotes EK, Penninx B, Hartikainen AL, Jarvelin MR, Gyllensten U, Boomsma DI, Campbell H, Wilson JF, Chanock SJ, Farrall M, Goel A, Medina-Gomez C, Rivadeneira F, Estrada K, Uitterlinden AG, Hofman A, Zillikens MC, den Heijer M, Kiemeney LA, Maschio A, Hall P, Tyrer J, Teumer A, Völzke H, Kovacs P, Tönjes A, Mangino M, Spector TD, Hayward C, Rudan I, Hall AS, Samani NJ, Attwood AP, Sambrook JG, Hung J, Palmer LJ, Lokki ML, Sinisalo J, Boucher G, Huikuri H, Lorentzon M, Ohlsson C, Eklund N, Eriksson JG, Barlassina C, Rivolta C, Nolte IM, Snieder H, Van der Klauw MM, Van Vliet-Ostaptchouk JV, Gejman PV, Shi J, Jacobs KB, Wang Z, Bakker SJ, Mateo Leach I, Navis G, van der Harst P, Martin NG, Medland SE, Montgomery GW, Yang J, Chasman DI, Ridker PM, Rose LM, Lehtimäki T, Raitakari O, Absher D, Iribarren C, Basart H, Hovingh KG, Hyppönen E, Power C, Anderson D, Beilby JP, Hui J, Jolley J, Sager H, Bornstein SR, Schwarz PE, Kristiansson K, Perola M, Lindström J, Swift AJ, Uusitupa M, Atalay M, Lakka TA, Rauramaa R, Bolton JL, Fowkes G, Fraser RM, Price JF, Fischer K, Krjutå Kov K, Metspalu A, Mihailov E, Langenberg C, Luan J, Ong KK, Chines PS, Keinanen-Kiukaanniemi SM, Saaristo TE, Edkins S, Franks PW, Hallmans G, Shungin D, Morris AD, Palmer CN, Erbel R, Moebus S, Nöthen MM, Pechlivanis S, Hveem K, Narisu N, Hamsten A, Humphries SE, Strawbridge RJ, Tremoli E, Grallert H, Thorand B, Illig T, Koenig W, Müller-Nurasyid M, Peters A, Boehm BO, Kleber ME, März W, Winkelmann BR, Kuusisto J, Laakso M, Arveiler D, Cesana G, Kuulasmaa K, Virtamo J, Yarnell JW, Kuh D, Wong A, Lind L, de Faire U, Gigante B, Magnusson PK, Pedersen NL, Dedoussis G, Dimitriou M, Kolovou G, Kanoni S, Stirrups K, Bonnycastle LL, Njølstad I, Wilsgaard T, Ganna A, Rehnberg E, Hingorani A, Kivimaki M, Kumari M, Assimes TL, Barroso I, Boehnke M, Borecki IB, Deloukas P, Fox CS, Frayling T, Groop LC, Haritunians T, Hunter D, Ingelsson E, Kaplan R, Mohlke KL, O'Connell JR, Schlessinger D, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, McCarthy MI, Hirschhorn JN, Qi L, Loos RJ, Lindgren CM, North KE, and Heid IM
- Subjects
- Body Height genetics, Body Mass Index, Body Weight genetics, Female, Genetic Loci, Genome, Human, Humans, Male, Polymorphism, Single Nucleotide, Waist Circumference genetics, Waist-Hip Ratio, Anthropometry methods, Body Weights and Measures, Genome-Wide Association Study, Sex Characteristics
- 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., Competing Interests: I have read the journal's policy and we have the following conflicts: Kari Stefansson, Valgerdur Steinthorsdottir, and Gudmar Thorleifsson are employed by deCODE Genetics with stock/stock options in the company. Inês Barroso and spouse own stock in Incyte Ltd and GlaxoSmithKline. Nilesh J Samani holds a Chair supported by the British Heart Foundation and is an NIHR Senior Investigator.
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- 2013
- Full Text
- View/download PDF
7. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
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Porcu E, Medici M, Pistis G, Volpato CB, Wilson SG, Cappola AR, Bos SD, Deelen J, den Heijer M, Freathy RM, Lahti J, Liu C, Lopez LM, Nolte IM, O'Connell JR, Tanaka T, Trompet S, Arnold A, Bandinelli S, Beekman M, Böhringer S, Brown SJ, Buckley BM, Camaschella C, de Craen AJ, Davies G, de Visser MC, Ford I, Forsen T, Frayling TM, Fugazzola L, Gögele M, Hattersley AT, Hermus AR, Hofman A, Houwing-Duistermaat JJ, Jensen RA, Kajantie E, Kloppenburg M, Lim EM, Masciullo C, Mariotti S, Minelli C, Mitchell BD, Nagaraja R, Netea-Maier RT, Palotie A, Persani L, Piras MG, Psaty BM, Räikkönen K, Richards JB, Rivadeneira F, Sala C, Sabra MM, Sattar N, Shields BM, Soranzo N, Starr JM, Stott DJ, Sweep FC, Usala G, van der Klauw MM, van Heemst D, van Mullem A, Vermeulen SH, Visser WE, Walsh JP, Westendorp RG, Widen E, Zhai G, Cucca F, Deary IJ, Eriksson JG, Ferrucci L, Fox CS, Jukema JW, Kiemeney LA, Pramstaller PP, Schlessinger D, Shuldiner AR, Slagboom EP, Uitterlinden AG, Vaidya B, Visser TJ, Wolffenbuttel BH, Meulenbelt I, Rotter JI, Spector TD, Hicks AA, Toniolo D, Sanna S, Peeters RP, and Naitza S
- Subjects
- Female, Genome-Wide Association Study, Humans, Hyperthyroidism blood, Hypothyroidism blood, Male, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Sex Characteristics, Signal Transduction genetics, Thyrotropin blood, Thyroxine genetics, Hyperthyroidism genetics, Hypothyroidism genetics, Thyroid Gland metabolism, Thyroid Gland physiopathology, Thyrotropin genetics, Thyroxine blood
- Abstract
Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
- Full Text
- View/download PDF
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