Details

Autor(en) / Beteiligte

• Arnold, Paul D
• Askland, Kathleen D
• Barlassina, Cristina
• Bellodi, Laura
• Bienvenu, O J
• Black, Donald
• Bloch, Michael
• Brentani, Helena
• Burton, Christie L
• Camarena, Beatriz
• Cappi, Carolina
• Cath, Danielle
• Cavallini, Maria
• Conti, David
• Cook, Edwin
• Coric, Vladimir
• Cullen, Bernadette A
• Cusi, Danielle
• Davis, Lea K
• Delorme, Richard
• Denys, Damiaan
• Derks, Eske
• Eapen, Valsamma
• Edlund, Christopher
• Erdman, Lauren
• Falkai, Peter
• Figee, Ma
• Fyer, Abigail J
• Geller, Daniel A
• Goes, Fernando S
• Grabe, Hans
• Grados, Marcos A
• Greenberg, Benjamin D
• Grünblatt, Edna
• Guo, Wei
• Hanna, Gregory L
• Hemmings, Sian
• Hounie, Ana G
• Jenicke, Michael
• Keenan, Clare
• Kennedy, James
• Khramtsova, Ekaterina A
• Konkashbaev, Anuar
• Knowles, James A
• Krasnow, Janice
• Lange, Cristophe
• Lanzagorta, Nuria
• Leboyer, Marion
• Lennertz, Leonhard
• Li, Bingbin
• Liang, K-Y
• Lochner, Christine
• Macciardi, Fabio
• Maher, Brion
• Maier, Wolfgang
• Marconi, Maurizio
• Mathews, Carol A
• Matthesien, Manuel
• McCracken, James T
• McLaughlin, Nicole C
• Miguel, Euripedes C
• Moessner, Rainald
• Murphy, Dennis L
• Neale, Benjamin
• Nestadt, Gerald
• Nestadt, Paul
• Nicolini, Humberto
• Nurmi, Ericka
• Osiecki, Lisa
• Pauls, David L
• Piacentini, John
• Posthuma, Danielle
• Pulver, Ann E
• Qin, H-D
• Rasmussen, Steven A
• Rauch, Scott
• Richter, Margaret A
• Riddle, Mark A
• Ripke, Stephan
• Ruhrmann, Stephan
• Sampaio, Aline S
• Samuels, Jack F
• Scharf, Jeremiah M
• Shugart, Yin Yao
• Smit, Jan
• Stein, Daniel
• Stewart, S Evelyn
• Turiel, Maurizio
• Vallada, Homero
• Veenstra-VanderWeele, Jeremy
• Wagner, Michael
• Walitza, Susanne
• Wang, Y
• Wendland, Jens
• Vulink, Nienke
• Yu, Dongmei
• Zai, Gwyneth

Titel

Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis

Ist Teil von

• Molecular psychiatry, 2018-05, Vol.23 (5), p.1181-1188

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Two obsessive–compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P -values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 ( P =7.1 × 10 −7 ; odds ratio (OR)=1.21; confidence interval (CI): 1.12–1.31, CASC8/CASC11 ), rs1030757 ( P =1.1 × 10 −6 ; OR=1.18; CI: 1.10–1.26, GRID2 ) and rs12504244 ( P =1.6 × 10 −6 ; OR=1.18; CI: 1.11–1.27, KIT ). Variants located in or near the genes ASB13 , RSPO4 , DLGAP1 , PTPRD , GRIK2 , FAIM2 and CDH20 , identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case–control status in the other by explaining 0.9% ( P =0.003) and 0.3% ( P =0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.