Genome-wide association study identifies new locus associated with OCD-Reference-Cited by-同舟云学术

Genome-wide association study identifies new locus associated with OCD

Published:2021-10-23 Issue: Volume: Page:
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Strom Nora I.^ORCID,Yu Dongmei^ORCID,Gerring Zachary F.^ORCID,Halvorsen Matthew W.^ORCID,Abdellaoui Abdel^ORCID,Rodriguez-Fontenla Cristina^ORCID,Sealock Julia M.^ORCID,Bigdeli Tim^ORCID,Coleman Jonathan R. I.^ORCID,Mahjani Behrang^ORCID,Thorp Jackson G.^ORCID,Bey Katharina^ORCID,Burton Christie L.^ORCID,Luykx Jurjen J.^ORCID,Zai Gwyneth^ORCID,Askland Kathleen D.^ORCID,Barlassina Cristina^ORCID,Nissen Judith Becker^ORCID,Bellodi Laura^ORCID,Bienvenu O. Joseph^ORCID,Black Donald^ORCID,Bloch Michael^ORCID,Boberg Julia^ORCID,Bosch Rosa^ORCID,Breen Michael^ORCID,Brennan Brian P.,Brentani Helena^ORCID,Buxbaum Joseph D.^ORCID,Bybjerg-Grauholm Jonas^ORCID,Byrne Enda M.^ORCID,Camarena Beatriz^ORCID,Camarena Adrian^ORCID,Cappi Carolina^ORCID,Carracedo Angel^ORCID,Casas Miguel^ORCID,Cavallini Maria C.^ORCID,Ciullo Valentina^ORCID,Cook Edwin H.^ORCID,Coric Vladimir,Cullen Bernadette A.^ORCID,De Schipper Elles J.^ORCID,Devlin Bernie^ORCID,Djurovic Srdjan^ORCID,Elias Jason A.,Erdman Lauren^ORCID,Estivil Xavier^ORCID,Falkenstein Martha J.,Fundin Bengt T.^ORCID,Gabrielsen Maiken E.^ORCID,Goes Fernando S.^ORCID,Grados Marco A.^ORCID,Grove Jakob,Guo Wei^ORCID,Haavik Jan^ORCID,Hagen Kristen,Havdahl Alexandra^ORCID,Hounie Ana G.^ORCID,Hucks Donald^ORCID,Hultman Christina^ORCID,Janecka Magdalena^ORCID,Jenike Michael^ORCID,Karlsson Elinor K.^ORCID,Klawohn Julia^ORCID,Klei Lambertus^ORCID,Krasnow Janice^ORCID,Krebs Kristi^ORCID,Krompinger Jason,Lanzagorta Nuria^ORCID,Macciardi Fabio^ORCID,Maher Brion^ORCID,McArthur Evonne^ORCID,McGregor Nathaniel^ORCID,McLaughlin Nicole C.^ORCID,Meier Sandra^ORCID,Miguel Euripedes C.^ORCID,Mulhern Maureen^ORCID,Nestadt Paul S.^ORCID,Nurmi Erika L.^ORCID,O’Connell Kevin S.^ORCID,Osiecki Lisa^ORCID,Palviainen Teemu^ORCID,Piras Fabrizio^ORCID,Piras Federica^ORCID,Pulver Ann E.^ORCID,Rabionet Raquel^ORCID,Ramirez Alfredo^ORCID,Rauch Scott^ORCID,Reichenberg Abraham^ORCID,Reichert Jennifer,Riddle Mark A.^ORCID,Ripke Stephan^ORCID,Sampaio Aline S.^ORCID,Schiele Miriam A.^ORCID,Sloofman Laura G.^ORCID,Smit Jan^ORCID,Sobell Janet L.^ORCID,Artigas María Soler^ORCID,Thomas Laurent F.^ORCID,Vallada Homero^ORCID,Veenstra-VanderWeele Jeremy^ORCID,Vulink Nienke N. C. C.^ORCID,Walker Christopher P.,Wang Ying^ORCID,Wendland Jens R.^ORCID,Winsvold Bendik S.^ORCID,Yao Yin^ORCID,Alonso Pino^ORCID,Berberich Götz^ORCID,Bulik Cynthia M.^ORCID,Cath Danielle^ORCID,Cusi Daniele^ORCID,Delorme Richard^ORCID,Denys Damiaan^ORCID,Eapen Valsamma^ORCID,Falkai Peter^ORCID,Fernandez Thomas V.^ORCID,Fyer Abby J.^ORCID,Geller Daniel A.^ORCID,Grabe Hans J.^ORCID,Greenberg Benjamin D.^ORCID,Hanna Gregory L.^ORCID,Hickie Ian M.^ORCID,Hougaard David M.,Kathmann Norbert^ORCID,Kennedy James^ORCID,Kung-Yee Liang^ORCID,Landén Mikael^ORCID,Le Hellard Stéphanie^ORCID,Leboyer Marion^ORCID,Lochner Christine^ORCID,McCracken James T.^ORCID,Medland Sarah E.^ORCID,Mortensen Preben B.,Neale Benjamin^ORCID,Nicolini Humberto^ORCID,Nordentoft Merete^ORCID,Pato Michele^ORCID,Pato Carlos^ORCID,Pauls David L.^ORCID,Pedersen Nancy L.^ORCID,Piacentini John^ORCID,Pittenger Christopher^ORCID,Posthuma Danielle^ORCID,Ramos-Quiroga Josep A^ORCID,Rasmussen Steven A.^ORCID,Ressler Kerry J.,Richter Margaret A.^ORCID,Rosário Maria C.^ORCID,Rosenberg David R.^ORCID,Ruhrmann Stephan^ORCID,Samuels Jack F.^ORCID,Sandin Sven^ORCID,Sandor Paul^ORCID,Spalletta Gianfranco^ORCID,Stein Dan J.^ORCID,Stewart S. Evelyn^ORCID,Storch Eric A.^ORCID,Stranger Barbara E.^ORCID,Turiel Maurizio^ORCID,Werge Thomas,Andreassen Ole A.^ORCID,Børglum Anders D.,Walitza Susanne^ORCID,Hansen Bjarne K. A.^ORCID,Rück Christian P.^ORCID,Martin Nicholas G.^ORCID,Milani Lili^ORCID,Mors Ole^ORCID,Reichborn-Kjennerud Ted^ORCID,Ribasés Marta^ORCID,Kvale Gerd^ORCID,Mataix-Cols David^ORCID,Domschke Katharina^ORCID,Grünblatt Edna^ORCID,Wagner Michael^ORCID,Zwart John-Anker^ORCID,Breen Gerome,Nestadt Gerald^ORCID,Metspalu Andres^ORCID,Kaprio Jaakko^ORCID,Arnold Paul D.^ORCID,Grice Dorothy E.^ORCID,Knowles James A.^ORCID,Ask Helga^ORCID,Verweij Karin J. H.^ORCID,Davis Lea K.^ORCID,Smit Dirk J. A.^ORCID,Crowley James J.^ORCID,Mathews Carol A.^ORCID,Derks Eske M.^ORCID,Scharf Jeremiah M.^ORCID,Mattheisen Manuel^ORCID

Abstract

Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this disorder.

Publisher

Cold Spring Harbor Laboratory

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