Common Genetic Variation and Age of Onset of Anorexia Nervosa

Watson, Hunna J.; Thornton, Laura M.; Yılmaz, Zeynep; Baker, Jessica H.; Coleman, Jonathan; 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 J.; Crowley, James J.; Danner, Unna N.; Zwaan, Martina de; Dedoussis, George; DeSocio, Janiece; Dick, Danielle M.; Dikeos, Dimitris; Dina, Christian; Djurovic, Srdjan; Dmitrzak‐Węglarz, 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; Foretová, Lenka; Forstner, Andreas J.; Frei, Oleksandr; Gallinger, Steven; Giegling, Ina; Giuranna, Johanna; Gonidakis, Fragiskos; Gorwood, Philip; Gratacòs, Mónica; Guillaume, Sébastien; Guo, Yiran; Hákonarson, Hákon; 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, Vladimí­r; Jiménez‐Murcia, Susana; Jones, Ian; Juliá, Antonio; Kalsi, Gursharan; Kaminská, Deborah; Kaprio, Jaakko; Karhunen, Leila; Kas, Martien; Keel, Pamela K.; Kennedy, James L.; Keski‐Rahkonen, Anna; Kiezebrink, Kirsty; Klareskog, Lars; Klump, Kelly L.; Knudsen, Gun Peggy; Via, Maria C. La; Hellard, Stéphanie Le; Leboyer, Marion; Liu, Dong; Lilenfeld, Lisa R.; Lin, Bochao; Lissowska, Jolanta; Luykx, Jurjen J.; Magistretti, Pierre J.; Maj, Mario; Marsal, Sara; Marshall, Christian R.; Mattingsdal, Morten; Meulenbelt, Ingrid; Micali, Nadia; Mitchell, Karen S.; Monteleone, Alessio Maria; Monteleone, Palmiero; Myers, R; Navrátilová, Marie; Ntalla, Ionna; O’Toole, Julie; Ophoff, Roel A.; Padyukov, Leonid; Pantel, Jacques; Papežová, Hana; Pinto, Dalila; Raevuori, Anu; Ramoz, Nicolás; 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; Landt, Margarita C T Slof-Op 't; Słopień, Agnieszka; Sorbi, Sandro; Świątkowska, Beata; Tortorella, Alfonso; Tozzi, Federica; Treasure, Janet; Τσίτσικα, Άρτεμις; Tyszkiewicz‐Nwafor, Marta; Tziouvas, Konstantinos; Elburg, Annemarie; Furth, Eric F. van; Walton, Esther; Widén, 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 Tidselbak; Parker, Richard; Petersen, Liselotte; Jordan, Jennifer; Kennedy, Martin A.; Wade, Tracey; Birgegård, Andreas; Lichtenstein, Paul; Landén, Mikael; Martin, Nicholas G.; Mortensen, Preben Bo; Breen, Gerome; Bulik, Cynthia M.

doi:10.1016/j.bpsgos.2021.09.001

Cited by 11 publications

(7 citation statements)

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“…This observation concurs with the literature, as a younger age at onset is known to be associated with more severe symptomatology [30,31]. The impact of age at onset on illness severity may stem from the aetiology of AN, which involves a complex interplay between genetics and the environment [32] and differs depending on age at onset; indeed, early-and typicalonset AN show distinct genetic correlation patterns with risk factors for the disease [33].…”

Section: Discussionsupporting

confidence: 90%

Food avoidance in anorexia nervosa: associated and predicting factors

et al. 2023

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Purpose Qualitative food avoidance is a significant issue in patients with anorexia nervosa (AN) and restoring diet diversity is an important part of the treatment process. We aimed to identify clinical factors which drive food avoidance and predict its maintenance in patients with AN. Methods In this multicentre longitudinal study, 130 female outpatients with AN were assessed before and after 4 months of care in clinical centres specialized in AN. We assessed levels of avoidance of 16 food items, as well as body mass index (BMI), eating disorder severity, symptoms of depression and anxiety, emotional state, daily-life functioning, and body image perception. Results We found that qualitative food avoidance was associated with the clinical severity of AN, anxiety and mood dimensions, and BMI- and body image-related factors. A younger age at onset predicted the maintenance of food avoidance after 4 months of treatment. Additional exploratory analyses suggested that anxiety and negative affect caused food avoidance more than the opposite. Conclusion Qualitative food avoidance can be an indicator of illness severity. During treatment, focusing on reducing anxiety and negative affect may be a way to indirectly reduce food avoidance and restore diet diversity. Level of evidence Level III: Evidence obtained from cohort or case-control analytic studies.

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Section: Discussionsupporting

confidence: 90%

Food avoidance in anorexia nervosa: associated and predicting factors

et al. 2023

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“….203 (5) Learning to learn -1,9 (1,9) vs .3 (1,7) .004 (7) 0,6 (1,9) vs 1,3 (1,2) .494 (5) Executive functions and attention (Nepsy II)…”

Section: Resultsmentioning

confidence: 99%

“…Animal Sorting (Nepsy II) 7,4 (3) vs 9,9 (1,5) .015 (7) 10,2 (1,2) vs 11 (2,2) .550 (5) Response set 3,5 (1,3) vs 5,4 (0,7) .006 (7) 5,5 (0,5) vs 5,5 (0,8) 1,00…”

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Individual Cognitive Remediation Therapy and Individual Emotion Skills Training for anorexia nervosa: a case series study in a paediatric ward

Marin

Cogo

Zanetti

et al. 2022

Preprint

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Purpose: Anorexia Nervosa (AN) is a life-threatening eating disorder (ED), with the highest incidence in young people (YP) aged 15-19 years. The COVID-19 pandemic impacted on the increase of AN cases requiring hospitalisation. Cognitive Remediation Therapy (CRT) and Cognitive Remediation and Emotion Skills Training (CREST) are brief interventions aimed at enhancing cognitive and emotion processing skills. They are feasible for adult and YP with AN in inpatient settings, but their use has not been yet explored in paediatric wards. Methods: A case series study with uncontrolled repeated measures design was conducted in a paediatric ward. Eight participants received two individual one-hour long CRT and then CREST sessions a week for ten weeks. A repeated measures design, consisting of neuropsychological tests and psychometric self-report questionnaires, was conducted at three time-points. Results: Significant differences (T0 vs T1) were found in cognitive flexibility [“Animal Sorting” t(7)=-3.208; p=0.015; “Response Set” (t(7)=-3.910; p=0.006);“Learning to learn” (t(7)=-4.259; p=0.004)]; in central coherence [“Central Coherence Index” t(7)=-2.401; p=0.047]; in executive functions [“Design” (t(7)=-3.208; p=0.015), “Semantic” (t(7)=-3.660; p=0.008), “Phonological fluency” (t(7)=-4.020; p=0.005), short-term verbal memory (t(5)=-11.00; p=<0.001) and decision making task [(HDT) t(7)=-3.826; p=0.006]. Regarding the emotion processing, significant differences were found in emotion recognition [“Theory of mind t(7)=-2.376; p=0.049] ,and self-awareness [“Noticing” t(7)=-2.220;p=0.062, and “Emotional awareness” t(7)=-2.391; p=0.048].These improvements were maintained at six-month follow-up. Conclusions: Individual CRT in conjunction with individual CREST is a feasible intervention for YP with AN in a paediatric ward. Studies involving larger samples and control groups in paediatric wards are warranted.

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“…22 Our analyses only considered participants of European ancestry, as the genetic discoveries were from predominantly European cohorts and the transferability of variants into non-European populations remains unknown. 52 It is worth noting that anorexia nervosa prevalence remains currently highest among European and Western cultures, is rapidly rising among young adolescent girls, 53 and is likely underdiagnosed in men and individuals from minoritized racial and ethnic groups, 52 necessitating future large investigations on early or late onset anorexia nervosa 54 and anorexia in non-European populations. We presented MR P values unadjusted for multiple testing because our study is exploratory in nature.…”

Section: Limitationsmentioning

confidence: 99%

The Role of Circadian Rhythms and Sleep in Anorexia Nervosa

Wilcox,

Paz,

Saxena

et al. 2024

JAMA Netw Open

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ImportanceObservational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by psychosocial comorbidities in these associations are unknown.ObjectivesTo investigate the association between anorexia nervosa and circadian and sleep traits through mendelian randomization and to test the associations between a polygenic risk score (PRS) for anorexia nervosa and sleep disorders in a clinical biobank.Design, Setting, and ParticipantsThis genetic association study used bidirectional 2-sample mendelian randomization with summary-level genetic associations between anorexia nervosa (from the Psychiatric Genomics Consortium) and chronotype and sleep traits (primarily from the UK Biobank). The inverse-variance weighted method, in addition to other sensitivity approaches, was used. From the clinical Mass General Brigham (MGB) Biobank (n = 47 082), a PRS for anorexia nervosa was calculated for each patient and associations were tested with prevalent sleep disorders derived from electronic health records. Patients were of European ancestry. All analyses were performed between February and August 2023.ExposuresGenetic instruments for anorexia nervosa, chronotype, daytime napping, daytime sleepiness, insomnia, and sleep duration.Main Outcomes and MeasuresChronotype, sleep traits, risk of anorexia nervosa, and sleep disorders derived from a clinical biobank.ResultsThe anorexia nervosa genome-wide association study included 16 992 cases (87.7%-97.4% female) and 55 525 controls (49.6%-63.4% female). Genetic liability for anorexia nervosa was associated with a more morning chronotype (β = 0.039; 95% CI, 0.006-0.072), and conversely, genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (β = 0.178; 95% CI, 0.042-0.315). Associations were robust in sensitivity and secondary analyses. Genetic liability for insomnia was associated with increased risk of anorexia nervosa (β = 0.369; 95% CI, 0.073-0.666); however, sensitivity analyses indicated bias due to horizontal pleiotropy. The MGB Biobank analysis included 47 082 participants with a mean (SD) age of 60.4 (17.0) years and 25 318 (53.8%) were female. A PRS for anorexia nervosa was associated with organic or persistent insomnia in the MGB Biobank (odds ratio, 1.10; 95% CI, 1.03-1.17). No associations were evident for anorexia nervosa with other sleep traits.Conclusions and RelevanceThe results of this study suggest that in contrast to other metabo-psychiatric diseases, anorexia nervosa is a morningness eating disorder and further corroborate findings implicating insomnia in anorexia nervosa. Future studies in diverse populations and with subtypes of anorexia nervosa are warranted.

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Common Genetic Variation and Age of Onset of Anorexia Nervosa

Cited by 11 publications

References 58 publications

Food avoidance in anorexia nervosa: associated and predicting factors

Food avoidance in anorexia nervosa: associated and predicting factors

Individual Cognitive Remediation Therapy and Individual Emotion Skills Training for anorexia nervosa: a case series study in a paediatric ward

The Role of Circadian Rhythms and Sleep in Anorexia Nervosa

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