Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Hoggart, C.J.; Venturini, G.; Mangino, M.; Gomez, F.; Ascari, G.; Zhao, J.H.; Teumer, A.; Winkler, T.W.; Tšernikova, N.; Luan, J.; Mihailov, E.; Ehret, G.B.; Zhang, W.; Lamparter, D.; Esko, T.; Macé, A.; Rüeger, S.; Bochud, P.; Barcella, M.; Dauvilliers, Y.; Benyamin, B.; Evans, D.M.; Hayward, C.; Lopez, M.F.; Franke, L.; Russo, A.; Heid, I.M.; Salvi, E.; Vendantam, S.; Arking, D.E.; Boerwinkle, E.; Chambers, J.C.; Fiorito, G.; Grallert, H.; Guarrera, S.; Homuth, G.; Huffman, J.E.; Porteous, D.; Berg, J.; Blackwood, D.; Campbell, H.; Cavanagh, J.; Connell, J.; Connor, M.; Cunningham Burley, S.; Deary, I.; Dominiczak, A.; Ellis, P.; Fitzpatrick, B.; Ford, I.; Gertz, R.; Grau, A.; Haddow, G.; Jackson, C.; Kerr, S.; Lindsay, R.; Mcgilchrist, M.; Mcintyre, D.; Morris, A.; Morton, R.; Muir, W.; Murray, G.; Palmer, C.; Pell, J.; Philp, A.; Porteous, D.; Porteous, M.; Procter, R.; Ralston, S.; Reid, D.; Sinnott, R.; Smith, B.; St Clair, D.; Sullivan, F.; Sweetland, M.; Ure, J.; Watt, G.; Wolf, R.; Wright, A.; De Bakker, P.; Bültmann, U.; Geleijnse, M.; Harst, P.V.D.; Koppelman, G.; Rosmalen, J.G.M.; Van Rossum, L.; Smidt, H.; Swertz, M.A.; Stolk, R.P.; Alizadeh, B.; De Boer, R.; Boezen, H.M.; Bruinenberg, M.; Franke, L.; Van Der Harst, P.; Hillege, H.; Van Der Klauw, M.; Navis, G.; Ormel, J.; Postma, D.; Rosmalen, J.; Slaets, J.; Snieder, H.; Stolk, R.; Wolffenbuttel, B.; Wijmenga, C.; Berndt, S.I.; Gustafsson, S.; Mägi, R.; Ganna, A.; Wheeler, E.; Feitosa, M.F.; Justice, A.E.; Monda, K.L.; Croteau Chonka, D.C.; Day, F.R.; Esko, T.; Fall, T.; Ferreira, T.; Gentilini, D.; Jackson, A.U.; Luan, J.; Randall, J.C.; Vedantam, S.; Willer, C.J.; Winkler, T.W.; Wood, A.R.; Workalemahu, T.; Hu, Y.; Lee, S.H.; Liang, L.; Lin, D.; Min, J.L.; Neale, B.M.; Thorleifsson, G.; Yang, J.; Albrecht, E.; Amin, N.; Bragg Gresham, J.L.; Cadby, G.; Den Heijer, M.; Eklund, N.; Fischer, K.; Goel, A.; Hottenga, J.; Huffman, J.E.; Jarick, I.; Johansson, A.; Johnson, T.; Kanoni, S.; Kleber, M.E.; König, I.R.; Kristiansson, K.; Kutalik, Z.; Lamina, C.; Lecoeur, C.; Li, G.; Mangino, M.; Mcardle, W.L.; Medina Gomez, C.; Müller Nurasyid, M.; Ngwa, J.S.; Nolte, I.M.; Paternoster, L.; Pechlivanis, S.; Perola, M.; Peters, M.J.; Preuss, M.; Rose, L.M.; Shi, J.; Shungin, D.; Smith, A.V.; Strawbridge, R.J.; Surakka, I.; Teumer, A.; Trip, M.D.; Tyrer, J.; Van Vliet Ostaptchouk, J.V.; Vandenput, L.; Waite, L.L.; Zhao, J.H.; Absher, D.; Asselbergs, F.W.; Atalay, M.; Attwood, A.P.; Balmforth, A.J.; Basart, H.; Beilby, J.; Bonnycastle, L.L.; Brambilla, P.; Bruinenberg, M.; Campbell, H.; Chasman, D.I.; Chines, P.S.; Collins, F.S.; Connell, J.M.; Cookson, W.; De Faire, U.; De Vegt, F.; Dei, M.; Dimitriou, M.; Edkins, S.; Estrada, K.; Evans, D.M.; Farrall, M.; Ferrario, M.M.; Ferrières, J.; Franke, L.; Frau, F.; Gejman, P.V.; Grallert, H.; Grönberg, H.; Gudnason, V.; Hall, A.S.; Hall, P.; Hartikainen, A.; Hayward, C.; Heard Costa, N.L.; Heath, A.C.; Hebebrand, J.; Homuth, G.; F. B., H.; Hunt, S.E.; Hyppönen, E.; Iribarren, C.; Jacobs, K.B.; Jansson, J.; Jula, A.; Kähönen, M.; Kathiresan, S.; Kee, F.; Khaw, K.; Kivimaki, M.; Koenig, W.; Kraja, A.T.; Kumari, M.; Karikuulasmaa, N.; Kuusisto, J.; Laitinen, J.H.; Lakka, T.A.; Langenberg, C.; Launer, L.J.; Lind, L.; Lindström, J.; Liu, J.; Liuzzi, A.; Lokki, M.; Lorentzon, M.; Madden, P.A.; Magnusson, P.K.; Manunta, P.; Marek, D.; März, W.; Leach, I.M.; Mcknight, B.; Medland, S.E.; Mihailov, E.; Milani, L.; Montgomery, G.W.; Mooser, V.; Mühleisen, T.W.; Munroe, P.B.; Musk, A.W.; Narisu, N.; Navis, G.; Nicholson, G.; Nohr, E.A.; Ong, K.K.; Oostra, B.A.; Palmer, C.N..A.; Palotie, A.; Peden, J.F.; Pedersen, N.; Peters, A.; Polasek, O.; Pouta, A.; Pramstaller, P.P.; Prokopenko, I.; Pütter, C.; Radhakrishnan, A.; Raitakari, O.; Rendon, A.; Rivadeneira, F.; Rudan, I.; Saaristo, T.E.; Sambrook, J.G.; Sanders, A.R.; Sanna, S.; Saramies, J.; Schipf, S.; Schreiber, S.; Schunkert, H.; Shin, S.; Signorini, S.; Sinisalo, J.; Skrobek, B.; Soranzo, N.; Stancakova, A.; Stark, K.; Stephens, J.C.; Stirrups, K.; Stolk, R.P.; Stumvoll, M.; Swift, A.J.; Theodoraki, E.V.; Thorand, B.; Tregouet, D.; Tremoli, E.; Van Der Klauw, M.M.; Van Meurs, J.B..J.; Vermeulen, S.H.; Viikari, J.; Virtamo, J.; Vitart, V.; Waeber, G.; Wang, Z.; Widen, E.; Wild, S.H.; Willemsen, G.; Winkelmann, B.R.; Witteman, J.C..M.; Wolffenbuttel, B.H..R.; Wong, A.; Wright, A.F.; Zillikens, M..C.; Amouyel, P.; Boehm, B.O.; Boerwinkle, E.; Boomsma, D.I.; Caulfield, M.J.; Chanock, S.J.; Cupples, L..A.; Cusi, D.; Dedoussis, G.V.; Erdmann, J.; Eriksson, J.G.; Franks, P.W.; Froguel, P.; Gieger, C.; Gyllensten, U.; Hamsten, A.; Harris, T.B.; Hengstenberg, C.; Hicks, A.A.; Hingorani, A.; Hinney, A.; Hofman, A.; Hovingh, K.G.; Hveem, K.; Illig, T.; Jarvelin, M.; Jöckel, K.; Keinanen Kiukaanniemi, S.M.; Kiemeney, L.A.; Kuh, D.; Laakso, M.; Lehtimäki, T.; Levinson, D.F.; Martin, N.G.; Metspalu, A.; Morris, A.D.; Nieminen, M.S.; Njølstad, I.; Ohlsson, C.; Oldehinkel, A.J.; Ouwehand, W.H.; Palmer, L.J.; Penninx, B.; Power, C.; Province, M.A.; Psaty, B.M.; Qi, L.; Rauramaa, R.; Ridker, P.M.; Ripatti, S.; Salomaa, V.; Samani, N.J.; Snieder, H.; Sørensen, T.I..A.; Spector, T.D.; Stefansson, K.; Tönjes, A.; Tuomilehto, J.; Uitterlinden, A.G.; Uusitupa, M.; Van Der Harst, P.; Vollenweider, P.; Wallaschofski, H.; Wareham, N.J.; Watkins, H.; Wichmann, H.; Wilson, J.F.; Abecasis, G.R.; Assimes, T.L.; Barroso, I.; Boehnke, M.; Borecki, I.B.; Deloukas, P.; Fox, C.S.; Frayling, T.; Groop, L.C.; Haritunian, T.; Heid, I.M.; Hunter, D.; Kaplan, R.C.; Karpe, F.; Miriammoffatt, N.; Mohlke, K.L.; O'Connell, J.R.; Pawitan, Y.; Schadt, E.E.; Schlessinger, D.; Steinthorsdottir, V.; Strachan, D.P.; Thorsteinsdottir, U.; Van Duijn, C.M.; Visscher, P.M.; Di Blasio, A.M.; Hirschhorn, J.N.; Lindgren, C.M.; Morris, A.P.; Meyre, D.; Scherag, A.; Mccarthy, M.I.; Speliotes, E.K.; North, K.E.; Loos, R.J..F.; Ingelsson, E.; Moradpour, D.; Iranzo, A.; Hebebrand, J.; Kemp, J.P.; Lammers, G.J.; Aubert, V.; Heim, M.H.; Martin, N.G.; Montgomery, G.W.; Peraita Adrados, R.; Santamaria, J.; Negro, F.; Schmidt, C.O.; Scott, R.A.; Spector, T.D.; Strauch, K.; Völzke, H.; Wareham, N.J.; Yuan, W.; Bell, J.T.; Chakravarti, A.; Kooner, J.S.; Peters, A.; Matullo, G.; Wallaschofski, H.; Whitfield, J.B.; Paccaud, F.; Vollenweider, P.; Bergmann, S.; Beckmann, J.S.; Tafti, M.; Hastie, N.D.; Cusi, D.; Bochud, M.; Frayling, T.M.; Metspalu, A.; Jarvelin, M.; Scherag, A.; Da Smith, G.; Borecki, I.B.; Rousson, V.; Hirschhorn, J.N.; Rivolta, C.; Loos, R.J..F.; Kutalik, Z.

doi:10.1371/journal.pgen.1004508

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ~4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity. © 2014 Hoggart et al.

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index / C.J. Hoggart, G. Venturini, M. Mangino, F. Gomez, G. Ascari, J.H. Zhao, A. Teumer, T.W. Winkler, N. Tšernikova, J. Luan, E. Mihailov, G.B. Ehret, W. Zhang, D. Lamparter, T. Esko, A. Macé, S. Rüeger, P. Bochud, M. Barcella, Y. Dauvilliers, B. Benyamin, D.M. Evans, C. Hayward, M.F. Lopez, L. Franke, A. Russo, I.M. Heid, E. Salvi, S. Vendantam, D.E. Arking, E. Boerwinkle, J.C. Chambers, G. Fiorito, H. Grallert, S. Guarrera, G. Homuth, J.E. Huffman, D. Porteous, J. Berg, D. Blackwood, H. Campbell, J. Cavanagh, J. Connell, M. Connor, S. Cunningham-Burley, I. Deary, A. Dominiczak, P. Ellis, B. FitzPatrick, I. Ford, R. Gertz, A. Grau, G. Haddow, C. Jackson, S. Kerr, R. Lindsay, M. McGilchrist, D. McIntyre, A. Morris, R. Morton, W. Muir, G. Murray, C. Palmer, J. Pell, A. Philp, D. Porteous, M. Porteous, R. Procter, S. Ralston, D. Reid, R. Sinnott, B. Smith, D. St Clair, F. Sullivan, M. Sweetland, J. Ure, G. Watt, R. Wolf, A. Wright, P. de Bakker, U. Bültmann, M. Geleijnse, P.V.D. Harst, G. Koppelman, J.G.M. Rosmalen, L. van Rossum, H. Smidt, M.A. Swertz, R.P. Stolk, B. Alizadeh, R. de Boer, H.M. Boezen, M. Bruinenberg, L. Franke, P. van der Harst, H. Hillege, M. van der Klauw, G. Navis, J. Ormel, D. Postma, J. Rosmalen, J. Slaets, H. Snieder, R. Stolk, B. Wolffenbuttel, C. Wijmenga, S.I. Berndt, S. Gustafsson, R. Mägi, A. Ganna, E. Wheeler, M.F. Feitosa, A.E. Justice, K.L. Monda, D.C. Croteau- Chonka, F.R. Day, T. Esko, T. Fall, T. Ferreira, D. Gentilini, A.U. Jackson, J. Luan, J.C. Randall, S. Vedantam, C.J. Willer, T.W. Winkler, A.R. Wood, T. Workalemahu, Y. Hu, S.H. Lee, L. Liang, D. Lin, J.L. Min, B.M. Neale, G. Thorleifsson, J. Yang, E. Albrecht, N. Amin, J.L. Bragg-Gresham, G. Cadby, M. den Heijer, N. Eklund, K. Fischer, A. Goel, J. Hottenga, J.E. Huffman, I. Jarick, A. Johansson, T. Johnson, S. Kanoni, M.E. Kleber, I.R. König, K. Kristiansson, Z. Kutalik, C. Lamina, C. Lecoeur, G. Li, M. Mangino, W.L. McArdle, C. Medina-Gomez, M. Müller-Nurasyid, J.S. Ngwa, I.M. Nolte, L. Paternoster, S. Pechlivanis, M. Perola, M.J. Peters, M. Preuss, L.M. Rose, J. Shi, D. Shungin, A.V. Smith, R.J. Strawbridge, I. Surakka, A. Teumer, M.D. Trip, J. Tyrer, J.V. Van Vliet-Ostaptchouk, L. Vandenput, L.L. Waite, J.H. Zhao, D. Absher, F.W. Asselbergs, M. Atalay, A.P. Attwood, A.J. Balmforth, H. Basart, J. Beilby, L.L. Bonnycastle, P. Brambilla, M. Bruinenberg, H. Campbell, D.I. Chasman, P.S. Chines, F.S. Collins, J.M. Connell, W. Cookson, U. de Faire, F. de Vegt, M. Dei, M. Dimitriou, S. Edkins, K. Estrada, D.M. Evans, M. Farrall, M.M. Ferrario, J. Ferrières, L. Franke, F. Frau, P.V. Gejman, H. Grallert, H. Grönberg, V. Gudnason, A.S. Hall, P. Hall, A. Hartikainen, C. Hayward, N.L. Heard-Costa, A.C. Heath, J. Hebebrand, G. Homuth, F.B. Hu, S.E. Hunt, E. Hyppönen, C. Iribarren, K.B. Jacobs, J. Jansson, A. Jula, M. Kähönen, S. Kathiresan, F. Kee, K. Khaw, M. Kivimaki, W. Koenig, A.T. Kraja, M. Kumari, n. KariKuulasmaa, J. Kuusisto, J.H. Laitinen, T.A. Lakka, C. Langenberg, L.J. Launer, L. Lind, J. Lindström, J. Liu, A. Liuzzi, M. Lokki, M. Lorentzon, P.A. Madden, P.K. Magnusson, P. Manunta, D. Marek, W. März, I.M. Leach, B. McKnight, S.E. Medland, E. Mihailov, L. Milani, G.W. Montgomery, V. Mooser, T.W. Mühleisen, P.B. Munroe, A.W. Musk, N. Narisu, G. Navis, G. Nicholson, E.A. Nohr, K.K. Ong, B.A. Oostra, C.N..A. Palmer, A. Palotie, J.F. Peden, N. Pedersen, A. Peters, O. Polasek, A. Pouta, P.P. Pramstaller, I. Prokopenko, C. Pütter, A. Radhakrishnan, O. Raitakari, A. Rendon, F. Rivadeneira, I. Rudan, T.E. Saaristo, J.G. Sambrook, A.R. Sanders, S. Sanna, J. Saramies, S. Schipf, S. Schreiber, H. Schunkert, S. Shin, S. Signorini, J. Sinisalo, B. Skrobek, N. Soranzo, A. Stancakova, K. Stark, J.C. Stephens, K. Stirrups, R.P. Stolk, M. Stumvoll, A.J. Swift, E.V. Theodoraki, B. Thorand, D. Tregouet, E. Tremoli, M.M. Van der Klauw, J.B..J. van Meurs, S.H. Vermeulen, J. Viikari, J. Virtamo, V. Vitart, G. Waeber, Z. Wang, E. Widen, S.H. Wild, G. Willemsen, B.R. Winkelmann, J.C..M. Witteman, B.H..R. Wolffenbuttel, A. Wong, A.F. Wright, M..C. Zillikens, P. Amouyel, B.O. Boehm, E. Boerwinkle, D.I. Boomsma, M.J. Caulfield, S.J. Chanock, L..A. Cupples, D. Cusi, G.V. Dedoussis, J. Erdmann, J.G. Eriksson, P.W. Franks, P. Froguel, C. Gieger, U. Gyllensten, A. Hamsten, T.B. Harris, C. Hengstenberg, A.A. Hicks, A. Hingorani, A. Hinney, A. Hofman, K.G. Hovingh, K. Hveem, T. Illig, M. Jarvelin, K. Jöckel, S.M. Keinanen-Kiukaanniemi, L.A. Kiemeney, D. Kuh, M. Laakso, T. Lehtimäki, D.F. Levinson, N.G. Martin, A. Metspalu, A.D. Morris, M.S. Nieminen, I. Njølstad, C. Ohlsson, A.J. Oldehinkel, W.H. Ouwehand, L.J. Palmer, B. Penninx, C. Power, M.A. Province, B.M. Psaty, L. Qi, R. Rauramaa, P.M. Ridker, S. Ripatti, V. Salomaa, N.J. Samani, H. Snieder, T.I..A. Sørensen, T.D. Spector, K. Stefansson, A. Tönjes, J. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, P. van der Harst, P. Vollenweider, H. Wallaschofski, N.J. Wareham, H. Watkins, H.-. Wichmann, J.F. Wilson, G.R. Abecasis, T.L. Assimes, I. Barroso, M. Boehnke, I.B. Borecki, P. Deloukas, C.S. Fox, T. Frayling, L.C. Groop, T. Haritunian, I.M. Heid, D. Hunter, R.C. Kaplan, F. Karpe, n. MiriamMoffatt, K.L. Mohlke, J.R. O'Connell, Y. Pawitan, E.E. Schadt, D. Schlessinger, V. Steinthorsdottir, D.P. Strachan, U. Thorsteinsdottir, C.M. van Duijn, P.M. Visscher, A.M. Di Blasio, J.N. Hirschhorn, C.M. Lindgren, A.P. Morris, D. Meyre, A. Scherag, M.I. McCarthy, E.K. Speliotes, K.E. North, R.J..F. Loos, E. Ingelsson, D. Moradpour, A. Iranzo, J. Hebebrand, J.P. Kemp, G.J. Lammers, V. Aubert, M.H. Heim, N.G. Martin, G.W. Montgomery, R. Peraita-Adrados, J. Santamaria, F. Negro, C.O. Schmidt, R.A. Scott, T.D. Spector, K. Strauch, H. Völzke, N.J. Wareham, W. Yuan, J.T. Bell, A. Chakravarti, J.S. Kooner, A. Peters, G. Matullo, H. Wallaschofski, J.B. Whitfield, F. Paccaud, P. Vollenweider, S. Bergmann, J.S. Beckmann, M. Tafti, N.D. Hastie, D. Cusi, M. Bochud, T.M. Frayling, A. Metspalu, M. Jarvelin, A. Scherag, G. Da Smith, I.B. Borecki, V. Rousson, J.N. Hirschhorn, C. Rivolta, R.J..F. Loos, Z. Kutalik. - In: PLOS GENETICS. - ISSN 1553-7390. - 10:7(2014 Jul), pp. e1004508.1-e1004508.12. [10.1371/journal.pgen.1004508]

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

C. J. Hoggart;G. Venturini;M. Mangino;F. Gomez;G. Ascari;J. H. Zhao;A. Teumer;T. W. Winkler;N. Tšernikova;J. Luan;E. Mihailov;G. B. Ehret;W. Zhang;D. Lamparter;T. Esko;A. Macé;S. Rüeger;P. Bochud;M. Barcella;Y. Dauvilliers;B. Benyamin;D. M. Evans;C. Hayward;M. F. Lopez;L. Franke;A. Russo;I. M. Heid;E. Salvi;S. Vendantam;D. E. Arking;E. Boerwinkle;J. C. Chambers;G. Fiorito;H. Grallert;S. Guarrera;G. Homuth;J. E. Huffman;D. Porteous;J. Berg;D. Blackwood;H. Campbell;J. Cavanagh;J. Connell;M. Connor;S. Cunningham Burley;I. Deary;A. Dominiczak;P. Ellis;B. FitzPatrick;I. Ford;R. Gertz;A. Grau;G. Haddow;C. Jackson;S. Kerr;R. Lindsay;M. McGilchrist;D. McIntyre;A. Morris;R. Morton;W. Muir;G. Murray;C. Palmer;J. Pell;A. Philp;D. Porteous;M. Porteous;R. Procter;S. Ralston;D. Reid;R. Sinnott;B. Smith;D. St Clair;F. Sullivan;M. Sweetland;J. Ure;G. Watt;R. Wolf;A. Wright;P. de Bakker;U. Bültmann;M. Geleijnse;P. V. D. Harst;G. Koppelman;J. G. M. Rosmalen;L. van Rossum;H. Smidt;M. A. Swertz;R. P. Stolk;B. Alizadeh;R. de Boer;H. M. Boezen;M. Bruinenberg;L. Franke;P. van der Harst;H. Hillege;M. van der Klauw;G. Navis;J. Ormel;D. Postma;J. Rosmalen;J. Slaets;H. Snieder;R. Stolk;B. Wolffenbuttel;C. Wijmenga;S. I. Berndt;S. Gustafsson;R. Mägi;A. Ganna;E. Wheeler;M. F. Feitosa;A. E. Justice;K. L. Monda;D. C. Croteau Chonka;F. R. Day;T. Esko;T. Fall;T. Ferreira;D. Gentilini;A. U. Jackson;J. Luan;J. C. Randall;S. Vedantam;C. J. Willer;T. W. Winkler;A. R. Wood;T. Workalemahu;Y. Hu;S. H. Lee;L. Liang;D. Lin;J. L. Min;B. M. Neale;G. Thorleifsson;J. Yang;E. Albrecht;N. Amin;J. L. Bragg Gresham;G. Cadby;M. den Heijer;N. Eklund;K. Fischer;A. Goel;J. Hottenga;J. E. Huffman;I. Jarick;A. Johansson;T. Johnson;S. Kanoni;M. E. Kleber;I. R. König;K. Kristiansson;Z. Kutalik;C. Lamina;C. Lecoeur;G. Li;M. Mangino;W. L. McArdle;C. Medina Gomez;M. Müller Nurasyid;J. S. Ngwa;I. M. Nolte;L. Paternoster;S. Pechlivanis;M. Perola;M. J. Peters;M. Preuss;L. M. Rose;J. Shi;D. Shungin;A. V. Smith;R. J. Strawbridge;I. Surakka;A. Teumer;M. D. Trip;J. Tyrer;J. V. Van Vliet Ostaptchouk;L. Vandenput;L. L. Waite;J. H. Zhao;D. Absher;F. W. Asselbergs;M. Atalay;A. P. Attwood;A. J. Balmforth;H. Basart;J. Beilby;L. L. Bonnycastle;P. Brambilla;M. Bruinenberg;H. Campbell;D. I. Chasman;P. S. Chines;F. S. Collins;J. M. Connell;W. Cookson;U. de Faire;F. de Vegt;M. Dei;M. Dimitriou;S. Edkins;K. Estrada;D. M. Evans;M. Farrall;M. M. Ferrario;J. Ferrières;L. Franke;F. Frau;P. V. Gejman;H. Grallert;H. Grönberg;V. Gudnason;A. S. Hall;P. Hall;A. Hartikainen;C. Hayward;N. L. Heard Costa;A. C. Heath;J. Hebebrand;G. Homuth;F. B. Hu;S. E. Hunt;E. Hyppönen;C. Iribarren;K. B. Jacobs;J. Jansson;A. Jula;M. Kähönen;S. Kathiresan;F. Kee;K. Khaw;M. Kivimaki;W. Koenig;A. T. Kraja;M. Kumari;n. KariKuulasmaa;J. Kuusisto;J. H. Laitinen;T. A. Lakka;C. Langenberg;L. J. Launer;L. Lind;J. Lindström;J. Liu;A. Liuzzi;M. Lokki;M. Lorentzon;P. A. Madden;P. K. Magnusson;P. Manunta;D. Marek;W. März;I. M. Leach;B. McKnight;S. E. Medland;E. Mihailov;L. Milani;G. W. Montgomery;V. Mooser;T. W. Mühleisen;P. B. Munroe;A. W. Musk;N. Narisu;G. Navis;G. Nicholson;E. A. Nohr;K. K. Ong;B. A. Oostra;C. N. . A. Palmer;A. Palotie;J. F. Peden;N. Pedersen;A. Peters;O. Polasek;A. Pouta;P. P. Pramstaller;I. Prokopenko;C. Pütter;A. Radhakrishnan;O. Raitakari;A. Rendon;F. Rivadeneira;I. Rudan;T. E. Saaristo;J. G. Sambrook;A. R. Sanders;S. Sanna;J. Saramies;S. Schipf;S. Schreiber;H. Schunkert;S. Shin;S. Signorini;J. Sinisalo;B. Skrobek;N. Soranzo;A. Stancakova;K. Stark;J. C. Stephens;K. Stirrups;R. P. Stolk;M. Stumvoll;A. J. Swift;E. V. Theodoraki;B. Thorand;D. Tregouet;E. Tremoli;M. M. Van der Klauw;J. B. . J. van Meurs;S. H. Vermeulen;J. Viikari;J. Virtamo;V. Vitart;G. Waeber;Z. Wang;E. Widen;S. H. Wild;G. Willemsen;B. R. Winkelmann;J. C. . M. Witteman;B. H. . R. Wolffenbuttel;A. Wong;A. F. Wright;M. . C. Zillikens;P. Amouyel;B. O. Boehm;E. Boerwinkle;D. I. Boomsma;M. J. Caulfield;S. J. Chanock;L. . A. Cupples;D. Cusi;G. V. Dedoussis;J. Erdmann;J. G. Eriksson;P. W. Franks;P. Froguel;C. Gieger;U. Gyllensten;A. Hamsten;T. B. Harris;C. Hengstenberg;A. A. Hicks;A. Hingorani;A. Hinney;A. Hofman;K. G. Hovingh;K. Hveem;T. Illig;M. Jarvelin;K. Jöckel;S. M. Keinanen Kiukaanniemi;L. A. Kiemeney;D. Kuh;M. Laakso;T. Lehtimäki;D. F. Levinson;N. G. Martin;A. Metspalu;A. D. Morris;M. S. Nieminen;I. Njølstad;C. Ohlsson;A. J. Oldehinkel;W. H. Ouwehand;L. J. Palmer;B. Penninx;C. Power;M. A. Province;B. M. Psaty;L. Qi;R. Rauramaa;P. M. Ridker;S. Ripatti;V. Salomaa;N. J. Samani;H. Snieder;T. I. . A. Sørensen;T. D. Spector;K. Stefansson;A. Tönjes;J. Tuomilehto;A. G. Uitterlinden;M. Uusitupa;P. van der Harst;P. Vollenweider;H. Wallaschofski;N. J. Wareham;H. Watkins;H. . Wichmann;J. F. Wilson;G. R. Abecasis;T. L. Assimes;I. Barroso;M. Boehnke;I. B. Borecki;P. Deloukas;C. S. Fox;T. Frayling;L. C. Groop;T. Haritunian;I. M. Heid;D. Hunter;R. C. Kaplan;F. Karpe;n. MiriamMoffatt;K. L. Mohlke;J. R. O'Connell;Y. Pawitan;E. E. Schadt;D. Schlessinger;V. Steinthorsdottir;D. P. Strachan;U. Thorsteinsdottir;C. M. van Duijn;P. M. Visscher;A. M. Di Blasio;J. N. Hirschhorn;C. M. Lindgren;A. P. Morris;D. Meyre;A. Scherag;M. I. McCarthy;E. K. Speliotes;K. E. North;R. J. . F. Loos;E. Ingelsson;D. Moradpour;A. Iranzo;J. Hebebrand;J. P. Kemp;G. J. Lammers;V. Aubert;M. H. Heim;N. G. Martin;G. W. Montgomery;R. Peraita Adrados;J. Santamaria;F. Negro;C. O. Schmidt;R. A. Scott;T. D. Spector;K. Strauch;H. Völzke;N. J. Wareham;W. Yuan;J. T. Bell;A. Chakravarti;J. S. Kooner;A. Peters;G. Matullo;H. Wallaschofski;J. B. Whitfield;F. Paccaud;P. Vollenweider;S. Bergmann;J. S. Beckmann;M. Tafti;N. D. Hastie;D. Cusi;M. Bochud;T. M. Frayling;A. Metspalu;M. Jarvelin;A. Scherag;G. Da Smith;I. B. Borecki;V. Rousson;J. N. Hirschhorn;C. Rivolta;R. J. . F. Loos;Z. Kutalik

2014

Abstract

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ~4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity. © 2014 Hoggart et al.

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Scheda completa (DC)

	Presenza di coautori internazionali
	
				Sì
			
	Lingua dell'articolo
	
				English
			
	Parole chiave
	
				Genetics ; Molecular Biology ; Ecology, Evolution, Behavior and Systematics ; Cancer Research; Genetics (clinical)
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore BIO/14 - Farmacologia
			
	Tipo
	
				Articolo
			
	Revisione (peer review)
	
				Esperti anonimi
			
	Classificazione della pubblicazione
	
				Pubblicazione scientifica
			
	Data di pubblicazione
	
				lug-2014
			
	Rivista in ANCE
	
				PLOS GENETICS
			
	Editore
	
				Public Library of Science
			
	Volume o annata
	
				10
			
	Fascicolo
	
				7
			
	Numero dell'articolo
	
				e1004508
			
	Pagina iniziale
	
				1
			
	Pagina finale
	
				12
			
	Numero di pagine
	
				12
			
	Stato di pubblicazione
	
				Pubblicato
			
	Rilevanza del periodico
	
				Periodico con rilevanza internazionale
			
	DOI
	
				https://dx.doi.org/10.1371/journal.pgen.1004508
			
	Banca dati sorgente
	
				scopus
pubmed
crossref
			
	Identificativo ISI
	
				WOS:000339902600049
			
	Identificativo SCOPUS
	
				2-s2.0-84905474692
			
	Identificativo PUBMED
	
				25078964
			
	Tipologia
	
				info:eu-repo/semantics/article
			
	Citazione
	
				Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index / C.J. Hoggart, G. Venturini, M. Mangino, F. Gomez, G. Ascari, J.H. Zhao, A. Teumer, T.W. Winkler, N. Tšernikova, J. Luan, E. Mihailov, G.B. Ehret, W. Zhang, D. Lamparter, T. Esko, A. Macé, S. Rüeger, P. Bochud, M. Barcella, Y. Dauvilliers, B. Benyamin, D.M. Evans, C. Hayward, M.F. Lopez, L. Franke, A. Russo, I.M. Heid, E. Salvi, S. Vendantam, D.E. Arking, E. Boerwinkle, J.C. Chambers, G. Fiorito, H. Grallert, S. Guarrera, G. Homuth, J.E. Huffman, D. Porteous, J. Berg, D. Blackwood, H. Campbell, J. Cavanagh, J. Connell, M. Connor, S. Cunningham-Burley, I. Deary, A. Dominiczak, P. Ellis, B. FitzPatrick, I. Ford, R. Gertz, A. Grau, G. Haddow, C. Jackson, S. Kerr, R. Lindsay, M. McGilchrist, D. McIntyre, A. Morris, R. Morton, W. Muir, G. Murray, C. Palmer, J. Pell, A. Philp, D. Porteous, M. Porteous, R. Procter, S. Ralston, D. Reid, R. Sinnott, B. Smith, D. St Clair, F. Sullivan, M. Sweetland, J. Ure, G. Watt, R. Wolf, A. Wright, P. de Bakker, U. Bültmann, M. Geleijnse, P.V.D. Harst, G. Koppelman, J.G.M. Rosmalen, L. van Rossum, H. Smidt, M.A. Swertz, R.P. Stolk, B. Alizadeh, R. de Boer, H.M. Boezen, M. Bruinenberg, L. Franke, P. van der Harst, H. Hillege, M. van der Klauw, G. Navis, J. Ormel, D. Postma, J. Rosmalen, J. Slaets, H. Snieder, R. Stolk, B. Wolffenbuttel, C. Wijmenga, S.I. Berndt, S. Gustafsson, R. Mägi, A. Ganna, E. Wheeler, M.F. Feitosa, A.E. Justice, K.L. Monda, D.C. Croteau- Chonka, F.R. Day, T. Esko, T. Fall, T. Ferreira, D. Gentilini, A.U. Jackson, J. Luan, J.C. Randall, S. Vedantam, C.J. Willer, T.W. Winkler, A.R. Wood, T. Workalemahu, Y. Hu, S.H. Lee, L. Liang, D. Lin, J.L. Min, B.M. Neale, G. Thorleifsson, J. Yang, E. Albrecht, N. Amin, J.L. Bragg-Gresham, G. Cadby, M. den Heijer, N. Eklund, K. Fischer, A. Goel, J. Hottenga, J.E. Huffman, I. Jarick, A. Johansson, T. Johnson, S. Kanoni, M.E. Kleber, I.R. König, K. Kristiansson, Z. Kutalik, C. Lamina, C. Lecoeur, G. Li, M. Mangino, W.L. McArdle, C. Medina-Gomez, M. Müller-Nurasyid, J.S. Ngwa, I.M. Nolte, L. Paternoster, S. Pechlivanis, M. Perola, M.J. Peters, M. Preuss, L.M. Rose, J. Shi, D. Shungin, A.V. Smith, R.J. Strawbridge, I. Surakka, A. Teumer, M.D. Trip, J. Tyrer, J.V. Van Vliet-Ostaptchouk, L. Vandenput, L.L. Waite, J.H. Zhao, D. Absher, F.W. Asselbergs, M. Atalay, A.P. Attwood, A.J. Balmforth, H. Basart, J. Beilby, L.L. Bonnycastle, P. Brambilla, M. Bruinenberg, H. Campbell, D.I. Chasman, P.S. Chines, F.S. Collins, J.M. Connell, W. Cookson, U. de Faire, F. de Vegt, M. Dei, M. Dimitriou, S. Edkins, K. Estrada, D.M. Evans, M. Farrall, M.M. Ferrario, J. Ferrières, L. Franke, F. Frau, P.V. Gejman, H. Grallert, H. Grönberg, V. Gudnason, A.S. Hall, P. Hall, A. Hartikainen, C. Hayward, N.L. Heard-Costa, A.C. Heath, J. Hebebrand, G. Homuth, F.B. Hu, S.E. Hunt, E. Hyppönen, C. Iribarren, K.B. Jacobs, J. Jansson, A. Jula, M. Kähönen, S. Kathiresan, F. Kee, K. Khaw, M. Kivimaki, W. Koenig, A.T. Kraja, M. Kumari, n. KariKuulasmaa, J. Kuusisto, J.H. Laitinen, T.A. Lakka, C. Langenberg, L.J. Launer, L. Lind, J. Lindström, J. Liu, A. Liuzzi, M. Lokki, M. Lorentzon, P.A. Madden, P.K. Magnusson, P. Manunta, D. Marek, W. März, I.M. Leach, B. McKnight, S.E. Medland, E. Mihailov, L. Milani, G.W. Montgomery, V. Mooser, T.W. Mühleisen, P.B. Munroe, A.W. Musk, N. Narisu, G. Navis, G. Nicholson, E.A. Nohr, K.K. Ong, B.A. Oostra, C.N..A. Palmer, A. Palotie, J.F. Peden, N. Pedersen, A. Peters, O. Polasek, A. Pouta, P.P. Pramstaller, I. Prokopenko, C. Pütter, A. Radhakrishnan, O. Raitakari, A. Rendon, F. Rivadeneira, I. Rudan, T.E. Saaristo, J.G. Sambrook, A.R. Sanders, S. Sanna, J. Saramies, S. Schipf, S. Schreiber, H. Schunkert, S. Shin, S. Signorini, J. Sinisalo, B. Skrobek, N. Soranzo, A. Stancakova, K. Stark, J.C. Stephens, K. Stirrups, R.P. Stolk, M. Stumvoll, A.J. Swift, E.V. Theodoraki, B. Thorand, D. Tregouet, E. Tremoli, M.M. Van der Klauw, J.B..J. van Meurs, S.H. Vermeulen, J. Viikari, J. Virtamo, V. Vitart, G. Waeber, Z. Wang, E. Widen, S.H. Wild, G. Willemsen, B.R. Winkelmann, J.C..M. Witteman, B.H..R. Wolffenbuttel, A. Wong, A.F. Wright, M..C. Zillikens, P. Amouyel, B.O. Boehm, E. Boerwinkle, D.I. Boomsma, M.J. Caulfield, S.J. Chanock, L..A. Cupples, D. Cusi, G.V. Dedoussis, J. Erdmann, J.G. Eriksson, P.W. Franks, P. Froguel, C. Gieger, U. Gyllensten, A. Hamsten, T.B. Harris, C. Hengstenberg, A.A. Hicks, A. Hingorani, A. Hinney, A. Hofman, K.G. Hovingh, K. Hveem, T. Illig, M. Jarvelin, K. Jöckel, S.M. Keinanen-Kiukaanniemi, L.A. Kiemeney, D. Kuh, M. Laakso, T. Lehtimäki, D.F. Levinson, N.G. Martin, A. Metspalu, A.D. Morris, M.S. Nieminen, I. Njølstad, C. Ohlsson, A.J. Oldehinkel, W.H. Ouwehand, L.J. Palmer, B. Penninx, C. Power, M.A. Province, B.M. Psaty, L. Qi, R. Rauramaa, P.M. Ridker, S. Ripatti, V. Salomaa, N.J. Samani, H. Snieder, T.I..A. Sørensen, T.D. Spector, K. Stefansson, A. Tönjes, J. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, P. van der Harst, P. Vollenweider, H. Wallaschofski, N.J. Wareham, H. Watkins, H.-. Wichmann, J.F. Wilson, G.R. Abecasis, T.L. Assimes, I. Barroso, M. Boehnke, I.B. Borecki, P. Deloukas, C.S. Fox, T. Frayling, L.C. Groop, T. Haritunian, I.M. Heid, D. Hunter, R.C. Kaplan, F. Karpe, n. MiriamMoffatt, K.L. Mohlke, J.R. O'Connell, Y. Pawitan, E.E. Schadt, D. Schlessinger, V. Steinthorsdottir, D.P. Strachan, U. Thorsteinsdottir, C.M. van Duijn, P.M. Visscher, A.M. Di Blasio, J.N. Hirschhorn, C.M. Lindgren, A.P. Morris, D. Meyre, A. Scherag, M.I. McCarthy, E.K. Speliotes, K.E. North, R.J..F. Loos, E. Ingelsson, D. Moradpour, A. Iranzo, J. Hebebrand, J.P. Kemp, G.J. Lammers, V. Aubert, M.H. Heim, N.G. Martin, G.W. Montgomery, R. Peraita-Adrados, J. Santamaria, F. Negro, C.O. Schmidt, R.A. Scott, T.D. Spector, K. Strauch, H. Völzke, N.J. Wareham, W. Yuan, J.T. Bell, A. Chakravarti, J.S. Kooner, A. Peters, G. Matullo, H. Wallaschofski, J.B. Whitfield, F. Paccaud, P. Vollenweider, S. Bergmann, J.S. Beckmann, M. Tafti, N.D. Hastie, D. Cusi, M. Bochud, T.M. Frayling, A. Metspalu, M. Jarvelin, A. Scherag, G. Da Smith, I.B. Borecki, V. Rousson, J.N. Hirschhorn, C. Rivolta, R.J..F. Loos, Z. Kutalik. - In: PLOS GENETICS. - ISSN 1553-7390. - 10:7(2014 Jul), pp. e1004508.1-e1004508.12. [10.1371/journal.pgen.1004508]
			
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						C.J. Hoggart, G. Venturini, M. Mangino, F. Gomez, G. Ascari, J.H. Zhao, A. Teumer, T.W. Winkler, N. Tšernikova, J. Luan, E. Mihailov, G.B. Ehret, W. Z...espandi
						
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