enigma ocd working group teleconference 22 nd of may 2015 1 pm gmt (greenwich mean time)...

ENIGMA OCD working group

Teleconference 22nd of May 2015

1 PM GMT (Greenwich Mean Time)Amsterdam/Barcelona/Berlin/Milan/Munich/Rome/Zurich 3 PM

Sao Paulo 10 AMTokyo/Kyoto/Seoul 10 PM

Cape Town 3 PMLos Angeles 6 AM

New York/Toronto/Michigan/Boston 9 AMBangalore 6.30 PM

Agenda1. Status subcortical meta-analysis2. Preliminary results subcortical meta-analysis3. Planning subcortical meta-analysis4. Future plans

Planning cortical meta-analysis Secondary research proposals Mega analysis

5. Hibar et al. IOCDFGC-ENIGMA1 paper6. Status grants and new grant opportunities7. Status GWAS (Jim/Carol)8. Future meetings

Please, send me ([email protected]) an email as soon as your site is‘online’, with the name of the person representing the site during the TC.

Take care of the quality of the TC: (un)mute your line by pressing 6!!

Agenda1. Status subcortical meta-analysis

Status per site and overall overview

2. Preliminary results meta-analysis3. Planning subcortical meta-analysis4. Future plans



Current status per sitePlease, check whether the information is

correct and let us know whether the planning (see slide 35) is feasible for your site.

Arnold (CAN)Analyses performed by Soreni(USA)

Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current status quality check please, proceed a.s.a.p.!

DNA material status•Part of the genotyping in house done/ part of the DNA samples are with Jim

Benedetti (ITA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current status FINISHED subcortical analyses

DNA material status•DNA samples not sent, still to discuss how to proceed (please contact Jim)

Beucke (DEU) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current status please send statistical analyses waiting for clinical data (done by June 1)

DNA material status•No DNA samples

Cheng (CHN)Analyses now performed by van den Heuvel (NLD)


Current status data is being quality checked (Vumc) Waiting for clinical data file (done within 2 wks)

DNA material status•Difficulties in transport of DNA samples

Denys (NLD) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•Samples sent to the Broad

Fitzgerald (USA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•DNA samples partially at SickKids/Jim

Gruner (USA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•DNA samples sent to Jim

van den Heuvel (NLD) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•DNA samples sent to the Broad/Jim

Hoexter (BRA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•DNA samples not send yet, will probably be send to Jim

Huyser (NLD)Analyses performed by van den Heuvel (NLD)




Koch (DEU) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Kwon (KOR) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•DNA samples sent to the Broad

Lazaro (ESP) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Mataix-Cols (SWE)Analyses performed by van den Heuvel (NLD)




Menchon (ESP) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Nakamae (JPN) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Nakao (JPN)Analyses performed by van den Heuvel (NLD)


Current status data is being quality checked (Vumc) waiting for clinical data file, please send a.s.a.p

DNA material status•Please update us regarding your DNA samples!!!

Reddy (IND) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current status quality checking please proceed a.s.a.p.! (expected to be done by May 29)


Rosenberg (USA)Analyses to be performed by van den Heuvel (NLD)


Current status preparing data transfer to VUmc Amsterdam (dependent on transfer speed not feasible anymore to include in first subcortical meta-analysis, but big sample of pediatric OCD, thus relevant to try)


Simpson (USA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output


DNA material status•Small N, still to be discussed with Jim

Soreni (USA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current status quality checking data, please proceed a.s.a.p.!


Spalletta (ITA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Stein (ZAF) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Tolin (USA) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Walitza (CHE) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Wang (CHN) Memorandum of understanding Putamen/pallidum images Histograms + Summarystats R statistical output



Memorandum of Understanding

Arnold Huyser Rosenberg Benedetti Koch Simpson Beucke Kwon Soreni Cheng Lazaro Spalletta Denys Mataix-Cols Stein Fitzgerald Menchon Tolin Gruner Nakamae Walitza van den Heuvel Nakao Wang Hoexter Reddy

Have sent putamen/pallidum images

Arnold Rosenberg

Benedetti Koch Simpson Beucke Kwon Soreni Cheng Lazaro Spalletta Denys Mataix-Cols Stein Fitzgerald Menchon Tolin Gruner Nakamae Walitza van den Heuvel Nakao Wang Hoexter Reddy Huyser

First instructionsHistograms & Summarystats

Arnold Nakao Rosenberg Cheng Reddy Soreni

Finished: Benedetti Huyser Nakao Beucke Koch Simpson Denys Kwon Spalletta Fitzgerald Lazaro Tolin Gruner Mataix-Cols Stein van den Heuvel Menchon Walitza Hoexter Nakamae Wang

Second instructionsR statistical analyses Arnold Nakao Rosenberg Beucke Reddy Soreni Cheng

Finished: Benedetti Koch Spalletta Denys Kwon Stein Fitzgerald Lazaro Tolin Gruner Nakamae

Walitza van den Heuvel Mataix-Cols Wang Hoexter Menchon Huyser Simpson

Overview

Agenda1. Status subcortical meta-analyses2. Preliminary results subcortical meta-analysis3. Planning subcortical meta-analysis4. Future plans



Preliminary results – Adult samplesPallidum OCD vs HC

Analyses controlled for age, sex and ICVP-value uncorrected: 0.041 Effect size (Cohen’s d): 0.12

Preliminary results Similar effect size for hippocampus (d=-

0.13; p=0.045) P value indicates trend significance (not

corrected for multiple comparisons) Moderator analysis showed no influence of

field strength No age by group interaction

Similar effect sizes (d=-0.14; p= 4.6x10-4) found in hippocampus volume of MDD patients vs HC

Planning meta-analysis for the subcortical volumes Remaining sites finished all steps for the subcortical analyses

in FS and statistical analyses in R> June 01, 2015

Final run meta-analysis (van den Heuvel/Boedhoe at Vumc)> July 01, 2015

July/August: extra time for additional analyses/checks Discussion on results during TC, August 27, 2015 Draft paper

> September 2015

Let’s try to meet these deadlines!Note: We have to set a deadline in order to proceed; it would be great to include all sites, but maybe some sites are not able to make it (it’s a pity for them, but these sites can probably join during next meta-analysis, e.g. cortical meta-analysis).

Agenda1. Status subcortical meta-analysis2. Preliminary results subcortical meta-analysis3. Planning subcortical meta-analysis4. Future plans

Planning cortical meta-analysisis dependent on the progress of the subcortical meta-analysis, but to be started a.s.a.p. (the recon-all also includes corticalsegmentation, so the analyses should take up less time)

Secondary research proposals Mega analysis


Secondary research proposals Approved (nobody objected)

DOMAIN (DTI in OCD Meta-analytic Investigation) – Piras et al

To approve (deadline objection May 22) Meta analysis of cortical structural covariance network

– Yun et al

Planned/suggested, but analysis plans not yet submitted: Resting state: Carles Soriano-Mas connectomics / graph analyses analysis: Kathrin Koch

Database for MeGa-analysis To do:

Ethical approval (a.s.a.p.!) Overall: van den Heuvel Each site: check local procedures

Fill Excel sheet clinical data (Premika will send format a.s.a.p.) Prepare sending data (all, who approved sharing raw data)

Based on our experience (OBIC and 1st year ENIGMA-OCD): building this database will cost a massive amount of work. Therefore, we will use ‘strict’ deadlines for data transfer. Sites that are not able to meet the deadlines might join at later stage / future analyses. So, please, start preparing a.s.a.p. (after receiving instructions)!

Agenda1. Status subcortical meta-analysis2. Preliminary results meta-analysis3. Planning subcortical meta-analysis4. Future plans5. Hibar et al. IOCDFGC-ENIGMA1 paper6. Status grants and new grant opportunities7. Status GWAS (Jim/Carol)8. Future meetings

Hibar et al. (in prep.)Title: Overlap between gene variants mediating risk for OCD and regional brain volumes(prepared for submission Biol Psychiatry)

Authors: The ENIGMA and IOCDF-GC Consortium, Derrek P. Hibar1, IOCDF-GC, ENIGMA2, Evelyn Stewart2,3,4, Odile A. van den Heuvel5, David L. Pauls2,3, James A. Knowles6, Dan J. Stein7, Paul M. Thompson1*

Note: ENIGMA-OCD working group not involved as co-authors, since imaging data was not from ENIGMA-OCD working group (no OCD scans involved in this analysis; genetic data was from IOCDFGC consortium). But: findings are very relevant for replicatiom study in our OCD sample!!

Hibar et al. (in prep.) ABSTRACT Background: A new collaborative effort between the International Obsessive Compulsive Disorder

Foundation Genetics Collaborative (IOCDF-GC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortia was formed to determine if there was evidence that (1) partially overlapping sets of genetic variants are associated with both OCD risk and regional brain volumes (pleiotropy), (2) the direction of a effect a genetic variant has on OCD risk variants is the same as its effect on regional brain volumes (concordance), and (3) genetic variants associated with specific brain volumes are significantly associated with OCD risk.

Methods: We used SNP Effect Concordance Analysis (SECA) to examine 6,946,379 SNPs that passed quality control from a recent large-scale GWAS of OCD (including 1,465 cases, 5,557 controls, and 299 trios), and recent genome-wide analyses of eight subcortical brain volumes (in 13,171 subjects). We determined the extent of genetic overlap between volume-associated SNPs and genetic variants associated with OCD risk.

Results: There was significant concordance between OCD risk variants and variants associated with greater nucleus accumbens (P = 2.0x10-4) and putamen volumes (P = 8.0x10-4). One variant influencing putamen volume (rs149154047; q=0.0375), one variant influencing amygdala volume (rs534371; q=0.00626) and two variants influencing thalamus volume (rs11872098; q=0.00687 and rs116331752; q=0.0374) were significantly associated with the risk for developing OCD, using conditional FDR.

Conclusion: These data are largely consistent with current neurocircuitry models of OCD, which have focused on the importance of fronto-striatal circuitry. Variants in the DLGAP1 gene (rs11872098) are associated with both thalamic volume and OCD risk, in line with the hypothesized role of altered glutamatergic signaling in OCD.

Agenda1. Status subcortical meta-analysis2. Preliminary results meta-analysis3. Planning subcortical meta-analysis4. Future plans5. Hibar et al. IOCDFGC-ENIGMA1 paper6. Status grants and new grant opportunities

1. Pending: Carles Soriano-Mas (OCD foundation)2. Pending: Fabrizio Piras (OCD foundation + national grant)3. Pending: Paul Arnold 4. Planned: Blair Simpson (NIH-grant for LMICs)5. Ideas: ??Note: feel free to submit also personal grants including ENIGMA-OCD data (but please,

propose/discuss plans prior to submission to prevent overlap with other analysis plans)

7. Status GWAS (Jim/Carol)8. Future meetings

Agenda1. Status subcortical meta-analysis2. Preliminary results meta-analysis3. Planning subcortical meta-analysis4. Future plans5. Hibar et al. IOCDFGC-ENIGMA1 paper6. Status grants and new grant opportunities7. Status GWAS (Jim/Carol)

1. Jim/Carol, could you please send overview of database and planning prior to TC?

2. All: please, let us (Premika/me) know what the status is of your DNA (material sent? If so to where (Broad or Jim Knowles?), material pending genotyping? material genotyped/received back?)

8. Future meetings

Agenda1. Status subcortical meta-analyses2. Preliminary results subcortical meta-analysis3. Planning subcortical meta-analysis4. Future plans5. Hibar et al ENIGMA paper6. Status grants7. status GWAS

8. future meetings ENIGMA working group PI’s

- June 2015: ENIGMA working group PI’s meeting, prior to HBM, Hawaii ENIGMA OCD working group members

- HBM 2015, Hawaii, June 14-18Please, email me to inform me about your conference plans, so that I

can plan an informal meeting (as we did in Toronto last week)

webpage See previous email for password (May 6). http://enigma.ini.usc.edu/ongoing/enigma-

ocd-working-group/enigma-ocd-members-page/

enigma ocd working group teleconference 22 nd of may 2015 1 pm gmt (greenwich mean time)...

Documents

statistical analyses

dna material statuspart

site isonline

clinical data file

quality checked vumc

overall overviewpreliminary

pmsao paulo

pmcape town