Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.
Details
Serval ID
serval:BIB_88CBAA3BF1CC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.
Journal
Molecular psychiatry
Working group(s)
GCAN, WTCCC3, GIANT, EGG, Price Foundation Collaborative Group, Children’s Hospital of Philadelphia/Price Foundation
Contributor(s)
Perica V.B., Franklin C.S., Floyd J.A., Thornton L.M., Huckins L.M., Southam L., Rayner N.W., Tachmazidou I., Klump K.L., Treasure J., Lewis C.M., Schmidt U., Tozzi F., Iezebrink K., Hebebrand J., Gorwood P., Adan R.A., Kas M.J., Favaro A., Santonastaso P., Fernández-Aranda F., Gratacos M., Rybakowski F., Dmitrzak-Weglarz M., Kaprio J., Keski-Rahkonen A., Raevuori-Helkamaa A., Van Furth E.F., Slof-Op't Landt M.C., Hudson J.I., Reichborn-Kjennerud T., Knudsen G.P., Monteleone P., Kaplan A.S., Karwautz A., Hakonarson H., Berrettini W.H., Guo Y., Li D., Schork N.J., Komaki G., Ando T., Inoko H., Esko T., Fischer K., Männik K., Metspalu A., Baker J.H., Cone R.D., Dackor J., DeSocio J.E., Hilliard C.E., O'Toole J.K., Pantel J., Szatkiewicz J.P., Taico C., Zerwas S., Trace S.E., Davis O.S., Helder S., Bühren K., Burghardt R., de Zwaan M., Egberts K., Ehrlich S., Herpertz-Dahlmann B., Herzog W., Imgart H., Scherag A., Scherag S., Zipfel S., Boni C., Ramoz N., Versini A., Brandys M.K., Danner U.N., de Kove C., Hendriks J., Koeleman B.P., Ophoff R.A., Strengman E., van Elburg A.A., Bruson A., Clementi M., Degortes D., Forzan M., Tenconi E., Docampo E., Escaramí G., Jiménez-Murcia S., Lissowska J., Rajewski A., Szeszenia-Dabrowska N., Slopien A., Hauser J., Karhunen L., Meulenbelt I., Slagboom P.E., Tortorella A., Maj M., Dedoussis G., Dikeos D., Gonidakis F., Tziouvas K., Tsitsika A., Papezova H., Slachtova L., Martaskova D., Kennedy J.L., Levitan R.D., Yilmaz Z., Huemer J., Koubek D., Merl E., Wagner G., Lichtenstein P., Breen G., Cohen-Woods S., Farmer A., McGuffin P., Cichon S., Giegling I., Herms S., Rujescu D., Schreiber S., Wichmann H.E., Dina C., Sladek R., Gambaro G., Soranzo N., Julia A., Marsal S., Rabionet R., Gaborieau V., Dick D.M., Palotie A., Ripatti S., Widén E., Andreassen O.A., Espeseth T., Lundervold A., Reinvang I., Steen V.M., Hellard S.L., Mattingsdal M., Ntalla I., Bencko V., Foretova L., Janout V., Navratilova M., Gallinger S., Pinto D., Scherer S.W., Aschauer H., Carlberg L., Schosser A., Alfredsson L., Ding B., Klareskog L., Padyukov L., Finan C., Kalsi G., Roberts M., Logan D.W., Peltonen L., Ritchie G.R., Barrett J.C., Estivill X., Hinney A., Sullivan P.F., Collier D.A., Zeggini E., Bulik C.M., Anderson C.A., Barrett J.C., Floyd J.A., Franklin C.S., McGinnis R., Soranzo N., Zeggini E., Sambrook J., Stephens J., Ouwehand W.H., McArdle W.L., Ring S.M., Strachan D.P., Alexander G., Bulik C.M., Collier D.A., Conlon P.J., Dominiczak A., Duncanson A., Hill A., Langford C., Lord G., Maxwell A.P., Morgan L., Peltonen L., Sandford R.N., Sheerin N., Vannberg F.O., Blackburn H., Chen W.M., Edkins S., Gillman M., Gray E., Hunt S.E., Nengut-Gumuscu S., Potter S., Rich S.S., Simpkin D., Whittaker P., de Bakker P., Bültmann U., Geleijnse M., Harst P.V., Koppelman G., Rosmalen J.G., 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., 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., Clair D.S., Sullivan F., Sweetland M., Ure J., Watt G., Wolf R., Wright A., 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.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., 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.L., Hayward C., Heard-Costa N.L., Heath A.C., Hebebrand J., Homuth G., Hu F.B., Hunt S.E., Hyppönen E., Iribarren C., Jacobs K.B., Jansson J.O., Jula A., Kähönen M., Kathiresan S., Kee F., Khaw K.T., Kivimaki M., Koenig W., Kraja A.T., Kumari M., Kuulasmaa K., Kuusisto J., Laitinen J.H., Lakka T.A., Langenberg C., Launer L.J., Lind L., Lindström J., Liu J., Liuzzi A., Lokki M.L., Lorentzon M., Madden P.A., Magnusson P.K., Manunta P., Marek D., März W., Mateo Leach I., 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., 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.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., 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., Wolffenbuttel B.H., Wong A., Wright A.F., Zillikens M., Amouyel P., Boehm B.O., Boerwinkle E., Boomsma D.I., Caulfield M.J., Chanock S.J., Cupples L., 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., Jöckel K.H., 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., 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., Moffatt M., 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., Adair L.S., Ang W., Atalay M., van Beijsterveldt T., Bergen N., Benke K., Berry D.J., Boomsma D.I., Bradfield J.P., Charoen P., Coin L., Cooper C., Cousminer D.L., Das S., Davis O.S., Dedoussis G.V., Elliott P., Estivill X., Evans D.M., Feenstra B., Flexeder C., Frayling T., Freathy R.M., Gaillard R., Geller F., Gillman M., Grant S.F., Groen-Blokhuis M., Goh L.K., Guxens M., Hakonarson H., Hattersley A.T., Haworth C.M., Hadley D., Hebebrand J., Heinrich J., Hinney A., Hirschhorn J.N., Hocher B., Holloway J.W., Holst C., Hottenga J.J., Horikoshi M., Huikari V., Hypponen E., Iñiguez C., Jaddoe V.W., Jarvelin M.R., Kaakinen M., Kilpeläinen T.O., Kirin M., Kowgier M., Lakka H.M., Lakka T.A., Lange L.A., Lawlor D.A., Lehtimäki T., Lewin A., Lindgren C., Lindi V., Maggi R., Marsh J., McCarthy M.I., Melbye M., Middeldorp C., Millwood I., Mohlke K.L., Mook-Kanamori D.O., Murray J.C., Nivard M., Nohr E.A., Ntalla I., Oken E., Ong K.K., O'Reilly P.F., Palmer L.J., Panoutsopoulou K., Pararajasingham J., Pearson E.R., Pennell C.E., Power C., Price T.S., Prokopenko I., Raitakari O.T., Rodriguez A., Salem R.M., Saw S.M., Scherag A., Sebert S., Siitonen N., Simell O., Sørensen T.I., Sovio U., Pourcain B.S., Strachan D.P., Sunyer J., Taal H.R., Teo Y.Y., Thiering E., Tiesler C., Timpson N.J., Uitterlinden A.G., Valcárcel B., Warrington N.M., White S., Widén E., Willemsen G., Wilson J.F., Yaghootkar H., Zeggini E., Elks C.E., Perry J.R., Sulem P., Chasman D.I., Franceschini N., He C., Lunetta K.L., Visser J.A., Byrne E.M., Cousminer D.L., Gudbjartsson D.F., Esko T., Feenstra B., Hottenga J.J., Koller D.L., Kutalik Z., Lin P., Mangino M., Marongiu M., McArdle P.F., Smith A.V., Stolk L., van Wingerden S.H., Zhao J.H., Albrecht E., Corre T., Ingelsson E., Hayward C., Magnusson P.K., Smith E.N., Ulivi S., Warrington M., Zgaga L., Alavere H., Amin N., Aspelund T., Bandinelli S., Barroso I., Berenson G.S., Bergmann S., Blackburn H., Boerwinkle E., Buring J.E., Busonero F., Campbell H., Chanock S.J., Chen W., Cornelis M.C., Couper D., Coviello A.D., d'Adamo P., de Faire U., de Geus E.J., Deloukas P., Döring A., Davey Smith G., Easton D.F., Eiriksdottir G., Emilsson V., Eriksson J., Ferrucci L., Folsom A.R., Foroud T., Garcia M., Gasparini P., Geller F., Gieger C., Gudnason V., Hall P., Hankinson S.E., Ferreli L., Heath A.C., Hernandez D.G., Hofman A., Hu F.B., Illig T., Järvelin M.R., Johnson A.D., Karasik D., Khaw K.T., Kiel D.P., Kilpeläinen T.O., Kolcic I., Kraft P., Launer L.J., Laven J.S., Li S., Liu J., Levy D., Martin N.G., McArdle W.L., Melbye M., Mooser V., Murray J.C., Murray S.S., Nalls M.A., Navarro P., Nelis M., Ness A.R., Northstone K., Oostra B.A., Peacock M., Palmer L.J., Palotie A., Paré G., Parker A.N., Pedersen N.L., Peltonen L., Pennell C.E., Pharoah P., Polasek O., Plump A.S., Pouta A., Porcu E., Rafnar T., Rice J.P., Ring S.M., Rivadeneira F., Rudan I., Sala C., Salomaa V., Sanna S., Schlessinger D., Schork N.J., Scuteri A., Segrè A.V., Shuldiner A.R., Soranzo N., Sovio U., Srinivasan S.R., Strachan D.P., Tammesoo M.L., Tikkanen E., Toniolo D., Tsui K., Tryggvadottir L., Tyrer J., Uda M., van Dam R.M., van Meurs J.B., Vollenweider P., Waeber G., Wareham N.J., Waterworth D.M., Weedon M.N., Wichmann H.E., Willemsen G., Wilson J.F., Wright A.F., Young L., Zhai G., Zhuang W.V., Bierut L.J., Boyd H.A., Crisponi L., Demerath E.W., van Duijn C.M., Econs M.J., Harris T.B., Hunter D.J., Loos R.J., Metspalu A., Montgomery G.W., Ridker P.M., Spector T.D., Streeten E.A., Stefansson K., Thorsteinsdottir U., Uitterlinden A.G., Widen E., Murabito J.M., Ong K.K., Murray A., Brandt H., Crawford S., Crow S., Fichter M.M., Halmi K.A., Johnson C., Kaplan A.S., Via M., Mitchell J., Strober M., Rotondo A., Treasure J., Woodside D.B., Bulik C.M., Keel P., Klump K.L., Lilenfeld L., Thornton L.M., Plotnicov K., Bergen A.W., Berrettini W., Kaye W., Magistretti P.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
02/2017
Peer-reviewed
Oui
Volume
22
Number
2
Pages
192-201
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10(-5), Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10(-06)/Pfemales: 3.45 × 10(-07)/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.
Pubmed
Create date
04/02/2017 16:51
Last modification date
20/08/2019 15:47
Usage data
