Abstract
Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism–h2) were 0.01–0.04 for age of onset, 0.16–0.25 for early-onset AN, and 0.17–0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
| Original language | English |
|---|---|
| Journal | Biological Psychiatry Global Open Science |
| Volume | 2 |
| Issue number | 4 |
| Pages (from-to) | 368-378 |
| Number of pages | 11 |
| ISSN | 2667-1743 |
| DOIs | |
| Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:© 2021 The Authors
Keywords
- Age of onset
- Anorexia nervosa
- Early-onset
- Genetic risk score
- Genetics
- GWAS
- Menarche
- Mendelian randomization
- Puberty
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Common Genetic Variation and Age of Onset of Anorexia Nervosa. / Watson, Hunna J.; Thornton, Laura M.; Yilmaz, Zeynep; Baker, Jessica H.; Coleman, Jonathan R.I.; Adan, Roger A.H.; Alfredsson, Lars; Andreassen, Ole A.; Ask, Helga; Berrettini, Wade H.; Boehnke, Michael; Boehm, Ilka; Boni, Claudette; Buehren, Katharina; Bulant, Josef; Burghardt, Roland; Chang, Xiao; Cichon, Sven; Cone, Roger D.; Courtet, Philippe; Crow, Scott; Crowley, James J.; Danner, Unna N.; de Zwaan, Martina; Dedoussis, George; DeSocio, Janiece E.; Dick, Danielle M.; Dikeos, Dimitris; Dina, Christian; Djurovic, Srdjan; Dmitrzak-Weglarz, Monika; Docampo-Martinez, Elisa; Duriez, Philibert; Egberts, Karin; Ehrlich, Stefan; Eriksson, Johan G.; Escaramís, Geòrgia; Esko, Tõnu; Estivill, Xavier; Farmer, Anne; Fernández-Aranda, Fernando; Fichter, Manfred M.; Föcker, Manuel; Foretova, Lenka; Forstner, Andreas J.; Frei, Oleksandr; Gallinger, Steven; Giegling, Ina; Giuranna, Johanna; Gonidakis, Fragiskos; Gorwood, Philip; Gratacòs, Mònica; Guillaume, Sébastien; Guo, Yiran; Hakonarson, Hakon; Hauser, Joanna; Havdahl, Alexandra; Hebebrand, Johannes; Helder, Sietske G.; Herms, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Hinney, Anke; Hübel, Christopher; Hudson, James I.; Imgart, Hartmut; Jamain, Stephanie; Janout, Vladimir; Jiménez-Murcia, Susana; Jones, Ian R.; Julià, Antonio; Kalsi, Gursharan; Kaminská, Deborah; Kaprio, Jaakko; Karhunen, Leila; Kas, Martien J.H.; Keel, Pamela K.; Kennedy, James L.; Keski-Rahkonen, Anna; Kiezebrink, Kirsty; Klareskog, Lars; Klump, Kelly L.; Knudsen, Gun Peggy S.; La Via, Maria C.; Le Hellard, Stephanie; Leboyer, Marion; Li, Dong; Lilenfeld, Lisa; Lin, Bochao; Lissowska, Jolanta; Luykx, Jurjen; Magistretti, Pierre; Maj, Mario; Marsal, Sara; Marshall, Christian R.; Mattingsdal, Morten; Meulenbelt, Ingrid; Micali, Nadia; Mitchell, Karen S.; Monteleone, Alessio Maria; Monteleone, Palmiero; Myers, Richard; Navratilova, Marie; Ntalla, Ionna; O'Toole, Julie K.; Ophoff, Roel A.; Padyukov, Leonid; Pantel, Jacques; Papežová, Hana; Pinto, Dalila; Raevuori, Anu; Ramoz, Nicolas; Reichborn-Kjennerud, Ted; Ricca, Valdo; Ripatti, Samuli; Ripke, Stephan; Ritschel, Franziska; Roberts, Marion; Rotondo, Alessandro; Rujescu, Dan; Rybakowski, Filip; Scherag, André; Scherer, Stephen W.; Schmidt, Ulrike; Scott, Laura J.; Seitz, Jochen; Silén, Yasmina; Šlachtová, Lenka; Slagboom, P. Eline; Slof-Op ‘t Landt, Margarita C.T.; Slopien, Agnieszka; Sorbi, Sandro; Świątkowska, Beata; Tortorella, Alfonso; Tozzi, Federica; Treasure, Janet; Tsitsika, Artemis; Tyszkiewicz-Nwafor, Marta; Tziouvas, Konstantinos; van Elburg, Annemarie A.; van Furth, Eric F.; Walton, Esther; Widen, Elisabeth; Zerwas, Stephanie; Zipfel, Stephan; Bergen, Andrew W.; Boden, Joseph M.; Brandt, Harry; Crawford, Steven; Halmi, Katherine A.; Horwood, L. John; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Mitchell, James E.; Olsen, Catherine M.; Pearson, John F.; Pedersen, Nancy L.; Strober, Michael; Werge, Thomas; Whiteman, David C.; Woodside, D. Blake; Gordon, Scott; Maguire, Sarah; Larsen, Janne T.; Parker, Richard; Petersen, Liselotte V.; Jordan, Jennifer; Kennedy, Martin; Wade, Tracey D.; Birgegård, Andreas; Lichtenstein, Paul; Landén, Mikael; Martin, Nicholas G.; Mortensen, Preben Bo; Breen, Gerome; Bulik, Cynthia M.
In: Biological Psychiatry Global Open Science, Vol. 2, No. 4, 2022, p. 368-378.Research output: Contribution to journal › Journal article › Research › peer-review
}
TY - JOUR
T1 - Common Genetic Variation and Age of Onset of Anorexia Nervosa
AU - Watson, Hunna J.
AU - Thornton, Laura M.
AU - Yilmaz, Zeynep
AU - Baker, Jessica H.
AU - Coleman, Jonathan R.I.
AU - Adan, Roger A.H.
AU - Alfredsson, Lars
AU - Andreassen, Ole A.
AU - Ask, Helga
AU - Berrettini, Wade H.
AU - Boehnke, Michael
AU - Boehm, Ilka
AU - Boni, Claudette
AU - Buehren, Katharina
AU - Bulant, Josef
AU - Burghardt, Roland
AU - Chang, Xiao
AU - Cichon, Sven
AU - Cone, Roger D.
AU - Courtet, Philippe
AU - Crow, Scott
AU - Crowley, James J.
AU - Danner, Unna N.
AU - de Zwaan, Martina
AU - Dedoussis, George
AU - DeSocio, Janiece E.
AU - Dick, Danielle M.
AU - Dikeos, Dimitris
AU - Dina, Christian
AU - Djurovic, Srdjan
AU - Dmitrzak-Weglarz, Monika
AU - Docampo-Martinez, Elisa
AU - Duriez, Philibert
AU - Egberts, Karin
AU - Ehrlich, Stefan
AU - Eriksson, Johan G.
AU - Escaramís, Geòrgia
AU - Esko, Tõnu
AU - Estivill, Xavier
AU - Farmer, Anne
AU - Fernández-Aranda, Fernando
AU - Fichter, Manfred M.
AU - Föcker, Manuel
AU - Foretova, Lenka
AU - Forstner, Andreas J.
AU - Frei, Oleksandr
AU - Gallinger, Steven
AU - Giegling, Ina
AU - Giuranna, Johanna
AU - Gonidakis, Fragiskos
AU - Gorwood, Philip
AU - Gratacòs, Mònica
AU - Guillaume, Sébastien
AU - Guo, Yiran
AU - Hakonarson, Hakon
AU - Hauser, Joanna
AU - Havdahl, Alexandra
AU - Hebebrand, Johannes
AU - Helder, Sietske G.
AU - Herms, Stefan
AU - Herpertz-Dahlmann, Beate
AU - Herzog, Wolfgang
AU - Hinney, Anke
AU - Hübel, Christopher
AU - Hudson, James I.
AU - Imgart, Hartmut
AU - Jamain, Stephanie
AU - Janout, Vladimir
AU - Jiménez-Murcia, Susana
AU - Jones, Ian R.
AU - Julià, Antonio
AU - Kalsi, Gursharan
AU - Kaminská, Deborah
AU - Kaprio, Jaakko
AU - Karhunen, Leila
AU - Kas, Martien J.H.
AU - Keel, Pamela K.
AU - Kennedy, James L.
AU - Keski-Rahkonen, Anna
AU - Kiezebrink, Kirsty
AU - Klareskog, Lars
AU - Klump, Kelly L.
AU - Knudsen, Gun Peggy S.
AU - La Via, Maria C.
AU - Le Hellard, Stephanie
AU - Leboyer, Marion
AU - Li, Dong
AU - Lilenfeld, Lisa
AU - Lin, Bochao
AU - Lissowska, Jolanta
AU - Luykx, Jurjen
AU - Magistretti, Pierre
AU - Maj, Mario
AU - Marsal, Sara
AU - Marshall, Christian R.
AU - Mattingsdal, Morten
AU - Meulenbelt, Ingrid
AU - Micali, Nadia
AU - Mitchell, Karen S.
AU - Monteleone, Alessio Maria
AU - Monteleone, Palmiero
AU - Myers, Richard
AU - Navratilova, Marie
AU - Ntalla, Ionna
AU - O'Toole, Julie K.
AU - Ophoff, Roel A.
AU - Padyukov, Leonid
AU - Pantel, Jacques
AU - Papežová, Hana
AU - Pinto, Dalila
AU - Raevuori, Anu
AU - Ramoz, Nicolas
AU - Reichborn-Kjennerud, Ted
AU - Ricca, Valdo
AU - Ripatti, Samuli
AU - Ripke, Stephan
AU - Ritschel, Franziska
AU - Roberts, Marion
AU - Rotondo, Alessandro
AU - Rujescu, Dan
AU - Rybakowski, Filip
AU - Scherag, André
AU - Scherer, Stephen W.
AU - Schmidt, Ulrike
AU - Scott, Laura J.
AU - Seitz, Jochen
AU - Silén, Yasmina
AU - Šlachtová, Lenka
AU - Slagboom, P. Eline
AU - Slof-Op ‘t Landt, Margarita C.T.
AU - Slopien, Agnieszka
AU - Sorbi, Sandro
AU - Świątkowska, Beata
AU - Tortorella, Alfonso
AU - Tozzi, Federica
AU - Treasure, Janet
AU - Tsitsika, Artemis
AU - Tyszkiewicz-Nwafor, Marta
AU - Tziouvas, Konstantinos
AU - van Elburg, Annemarie A.
AU - van Furth, Eric F.
AU - Walton, Esther
AU - Widen, Elisabeth
AU - Zerwas, Stephanie
AU - Zipfel, Stephan
AU - Bergen, Andrew W.
AU - Boden, Joseph M.
AU - Brandt, Harry
AU - Crawford, Steven
AU - Halmi, Katherine A.
AU - Horwood, L. John
AU - Johnson, Craig
AU - Kaplan, Allan S.
AU - Kaye, Walter H.
AU - Mitchell, James E.
AU - Olsen, Catherine M.
AU - Pearson, John F.
AU - Pedersen, Nancy L.
AU - Strober, Michael
AU - Werge, Thomas
AU - Whiteman, David C.
AU - Woodside, D. Blake
AU - Gordon, Scott
AU - Maguire, Sarah
AU - Larsen, Janne T.
AU - Parker, Richard
AU - Petersen, Liselotte V.
AU - Jordan, Jennifer
AU - Kennedy, Martin
AU - Wade, Tracey D.
AU - Birgegård, Andreas
AU - Lichtenstein, Paul
AU - Landén, Mikael
AU - Martin, Nicholas G.
AU - Mortensen, Preben Bo
AU - Breen, Gerome
AU - Bulik, Cynthia M.
N1 - Publisher Copyright: © 2021 The Authors
PY - 2022
Y1 - 2022
N2 - Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism–h2) were 0.01–0.04 for age of onset, 0.16–0.25 for early-onset AN, and 0.17–0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
AB - Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism–h2) were 0.01–0.04 for age of onset, 0.16–0.25 for early-onset AN, and 0.17–0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
KW - Age of onset
KW - Anorexia nervosa
KW - Early-onset
KW - Genetic risk score
KW - Genetics
KW - GWAS
KW - Menarche
KW - Mendelian randomization
KW - Puberty
U2 - 10.1016/j.bpsgos.2021.09.001
DO - 10.1016/j.bpsgos.2021.09.001
M3 - Journal article
C2 - 36324647
AN - SCOPUS:85129769148
VL - 2
SP - 368
EP - 378
JO - Biological Psychiatry Global Open Science
JF - Biological Psychiatry Global Open Science
SN - 2667-1743
IS - 4
ER -