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., Tsernikova, N., Luan, J., Mihailov, E., Ehret, G. B., Zhang, W., Lamparter, D., Esko, T., Mace, A., Rueger, S., Bochud, P.-Y., 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., Bultmann, 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., Magi, 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.-J., Lee, S.H., Liang, L., Lin, D.-Y., 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.-J., Huffman, J. E., Jarick, I., Johansson, A., Johnson, T., Kanoni, S., Kleber, M. E., Konig, I. R., Kristiansson, K., Kutalik, Z., Lamina, C., Lecoeur, C., Li, G., Mangino, M., McArdle, W. L., Medina-Gomez, C., Muller-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., Ferrieres, J., Franke, L., Frau, F., Gejman, P. V., Grallert, H., Gronberg, H., Gudnason, V., Hall, A.S., Hall, P., Hartikainen, A.-L., Hayward, C., Heard-Costa, N. L., Heath, A. C., Hebebrand, J., Homuth, G., Hu, F. B., Hunt, S. E., Hypponen, E., Iribarren, C., Jacobs, K. B., Jansson, J.-O., Jula, A., Kahonen, M., Kathiresan, S., Kee, F., Khaw, K.-T., Kivimaki, M., Koenig, W., Kraja, A.T., Kumari, M., KariKuulasmaa, Kuusisto, J., Laitinen, J.H., Lakka, T. A., Langenberg, C., Launer, L. J., Lind, L., Lindstrom, J., Liu, J., Liuzzi, A., Lokki, M.-L., Lorentzon, M., Madden, P. A., Magnusson, P. K., Manunta P., Marek, D., Marz, W., Leach, I. M., McKnight, B., Medland, S. E., Mihailov, E., Milani, L., Montgomery, G. W., Mooser, V., Muhleisen, 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., Putter 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.-Y., 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.-A., 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.-R., Jockel K.-H., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kuh D., Laakso M., Lehtimaki T., Levinson D.F., Martin N.G., Metspalu A., Morris A.D., Nieminen M.S., Njolstad 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., Sorensen T.I.A., Spector T.D., Stefansson K., Tonjes A., Tuomilehto J., Uitterlinden A.G., Uusitupa M., van der Harst P., Vollenweider P., Wallaschofski H., Wareham N.J., Watkins H., Wichmann H.-E., 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, 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., Volzke 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.-R., Scherag A., Da Smith G., Borecki I.B., Rousson V., Hirschhorn J.N., Rivolta C., Loos R.J.F. and Kutalik Z. (2014) Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index. PLoS Genetics, 10 7: 1-12. doi:10.1371/journal.pgen.1004508


Author Hoggart, C. J.
Venturini, G.
Mangino, M.
Gomez, F.
Ascari, G.
Zhao, J.H.
Teumer, A.
Winkler, T. W.
Tsernikova, N.
Luan, J.
Mihailov, E.
Ehret, G. B.
Zhang, W.
Lamparter, D.
Esko, T.
Mace, A.
Rueger, S.
Bochud, P.-Y.
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.
Bultmann, 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.
Magi, 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.-J.
Lee, S.H.
Liang, L.
Lin, D.-Y.
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.-J.
Huffman, J. E.
Jarick, I.
Johansson, A.
Johnson, T.
Kanoni, S.
Kleber, M. E.
Konig, I. R.
Kristiansson, K.
Kutalik, Z.
Lamina, C.
Lecoeur, C.
Li, G.
Mangino, M.
McArdle, W. L.
Medina-Gomez, C.
Muller-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.
Ferrieres, J.
Franke, L.
Frau, F.
Gejman, P. V.
Grallert, H.
Gronberg, H.
Gudnason, V.
Hall, A.S.
Hall, P.
Hartikainen, A.-L.
Hayward, C.
Heard-Costa, N. L.
Heath, A. C.
Hebebrand, J.
Homuth, G.
Hu, F. B.
Hunt, S. E.
Hypponen, E.
Iribarren, C.
Jacobs, K. B.
Jansson, J.-O.
Jula, A.
Kahonen, M.
Kathiresan, S.
Kee, F.
Khaw, K.-T.
Kivimaki, M.
Koenig, W.
Kraja, A.T.
Kumari, M.
KariKuulasmaa
Kuusisto, J.
Laitinen, J.H.
Lakka, T. A.
Langenberg, C.
Launer, L. J.
Lind, L.
Lindstrom, J.
Liu, J.
Liuzzi, A.
Lokki, M.-L.
Lorentzon, M.
Madden, P. A.
Magnusson, P. K.
Manunta P.
Marek, D.
Marz, W.
Leach, I. M.
McKnight, B.
Medland, S. E.
Mihailov, E.
Milani, L.
Montgomery, G. W.
Mooser, V.
Muhleisen, 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.
Putter 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.-Y.
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.-A.
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.-R.
Jockel K.-H.
Keinanen-Kiukaanniemi S.M.
Kiemeney L.A.
Kuh D.
Laakso M.
Lehtimaki T.
Levinson D.F.
Martin N.G.
Metspalu A.
Morris A.D.
Nieminen M.S.
Njolstad 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.
Sorensen T.I.A.
Spector T.D.
Stefansson K.
Tonjes A.
Tuomilehto J.
Uitterlinden A.G.
Uusitupa M.
van der Harst P.
Vollenweider P.
Wallaschofski H.
Wareham N.J.
Watkins H.
Wichmann H.-E.
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
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.
Volzke 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.-R.
Scherag A.
Da Smith G.
Borecki I.B.
Rousson V.
Hirschhorn J.N.
Rivolta C.
Loos R.J.F.
Kutalik Z.
Title Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7404
1553-7390
Publication date 2014
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1004508
Open Access Status DOI
Volume 10
Issue 7
Start page 1
End page 12
Total pages 12
Place of publication San Francisco, CA, U.S.A.
Publisher Public Library of Science
Collection year 2015
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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