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. 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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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	Parole chiave
	
			Genetics ; Molecular Biology ; Ecology, Evolution, Behavior and Systematics ; Cancer Research; Genetics (clinical)
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore BIO/14 - Farmacologia
		
	Data di pubblicazione
	
			lug-2014
		
	Rivista in ANCE
	
			PLOS GENETICS
		
	DOI
	
			https://dx.doi.org/10.1371/journal.pgen.1004508
		
	Tipologia
	
			Article (author)
		
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			01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/239643

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