Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Yao, S.; Kuja-Halkola, R.; Martin, J.; Lu, Y.; Lichtenstein, P.; Hubel, C.; Almqvist, C.; Magnusson, P. K.; Bulik, C. M.; Larsson, H.; Norring, C.; Birgegard, A.; Norring, C.; Birgegard, A.; Almqvist, C.; Larsson, H.; Martin, J.; Hubel, C.; Yilmaz, Z.; Watson, H.; Baker, J.; Thornton, L. M.; Bulik, C. M.; Bulik, C. M.; Adan, R.; Ando, T.; Baker, J.; Bergen, A.; Berrettini, W.; Birgegard, A.; Boni, C.; Boraska Perica, V.; Brandt, H.; Burghardt, R.; Cassina, M.; Cesta, C.; Clementi, M.; Coleman, J.; Cone, R.; Courtet, P.; Crawford, S.; Crow, S.; Crowley, J.; Danner, U.; Davis, O.; de Zwaan, M.; Dedoussis, G.; Degortes, D.; Desocio, J.; Dick, D.; Dikeos, D.; Dmitrzak-Weglarz, M.; Docampo, E.; Egberts, K.; Ehrlich, S.; Escaramis, G.; Esko, T.; Estivill, X.; Favaro, A.; Fernandez-Aranda, F.; Fichter, M.; Finan, C.; Fischer, K.; Focker, M.; Foretova, L.; Forzan, M.; Franklin, C.; Gaspar, H.; Gonidakis, F.; Gorwood, P.; Gratacos, M.; Guillaume, S.; Guo, Y.; Hakonarson, H.; Halmi, K.; Hatzikotoulas, K.; Hauser, J.; Hebebrand, J.; Helder, S.; Hendriks, J.; Herpertz-Dahlmann, B.; Herzog, W.; Hilliard, C.; Hinney, A.; Huckins, L.; Hudson, J.; Huemer, J.; Imgart, H.; Inoko, H.; Jimenez-Murcia, S.; Johnson, C.; Jordan, J.; Jureus, A.; Kalsi, G.; Kaminska, D.; Kaplan, A.; Kaprio, J.; Karhunen, L.; Karwautz, A.; Kas, M.; Kaye, W.; Kennedy, J.; Kennedy, M.; Keski-Rahkonen, A.; Kiezebrink, K.; Kim, Y. -R.; Klump, K.; Knudsen, G. P.; Koeleman, B.; Koubek, D.; La Via, M.; Landen, M.; Levitan, R.; Li, D.; Lichtenstein, P.; Lilenfeld, L.; Lissowska, J.; Magistretti, P.; Maj, M.; Mannik, K.; Martin, N.; Mcdevitt, S.; Mcguffin, P.; Merl, E.; Metspalu, A.; Meulenbelt, I.; Micali, N.; Mitchell, J.; Mitchell, K.; Monteleone, P.; Monteleone, A. M.; Mortensen, P.; Munn-Chernoff, M.; Nacmias, B.; Nilsson, I.; Norring, C.; Ntalla, I.; O'Toole, J.; Pantel, J.; Papezova, H.; Parker, R.; Rabionet, R.; Raevuori, A.; Rajewski, A.; Ramoz, N.; Rayner, N. W.; Reichborn-Kjennerud, T.; Ricca, V.; Ripke, S.; Ritschel, F.; Roberts, M.; Rotondo, A.; Rybakowski, F.; Santonastaso, P.; Scherag, A.; Schmidt, U.; Schork, N.; Schosser, A.; Seitz, J.; Slachtova, L.; Slagboom, P. E.; Slof-Op't Landt, M.; Slopien, A.; Smith, T.; Sorbi, S.; Strengman, E.; Strober, M.; Sullivan, P.; Szatkiewicz, J.; Szeszenia-Dabrowska, N.; Tachmazidou, I.; Tenconi, E.; Thornton, L.; Tortorella, A.; Tozzi, F.; Treasure, J.; Tsitsika, A.; Tziouvas, K.; van Elburg, A.; van Furth, E.; Wade, T.; Wagner, G.; Walton, E.; Watson, H.; Woodside, D. B.; Yao, S.; Yilmaz, Z.; Zeggini, E.; Zerwas, S.; Zipfel, S.; Alfredsson, L.; Andreassen, O.; Aschauer, H.; Barrett, J.; Bencko, V.; Carlberg, L.; Cichon, S.; Cohen-Woods, S.; Dina, C.; Ding, B.; Espeseth, T.; Floyd, J.; Gallinger, S.; Gambaro, G.; Giegling, I.; Herms, S.; Janout, V.; Julia, A.; Klareskog, L.; Le Hellard, S.; Leboyer, M.; Lundervold, A.; Marsal, S.; Mattingsdal, M.; Navratilova, M.; Ophoff, R.; Palotie, A.; Pinto, D.; Ripatti, S.; Rujescu, D.; Scherer, S.; Scott, L.; Sladek, R.; Soranzo, N.; Southam, L.; Steen, V.; Wichmann, H. -E.; Widen, E.; Breen, G.; Bulik, C.

doi:10.1016/j.biopsych.2019.04.036

Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI =.31,.42) than with AN (.14, 95% CI =.05,.22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.