GResU - GWAS Research Unit

Research unit for statistical genetics for common variant analyses (GWAS)

GResU is a service oriented research unit supporting statistical analysis of common variants, primarily genome wide association studies (GWAS). We offer support for all stages, from developing an analysis plan to preparing results for publication.

GResU analysts (currently one Heisenberg Professor, one staff scientist, 3 PhD students and 3 student assistants) have extensive experience dealing with hundreds of GWAS cohorts within various consortia and contributed to 150+ publications, many of them in leading analytic roles, most prominently in the discovery of more than 100 genomic loci for schizophrenia in 2014. As one of the central analysis groups of the Psychiatric Genomics Consortium (PGC), we are always evaluating and incorporating new methods into our pipeline as they become available.

We are currently collaborating with a wide range of medical research groups (for a detailed list see the end of the page).

We also conduct our own studies, formerly BePS (Berlin Psychosis Study), now BRIDGE-S (Berlin Research Initiative for Diagnostics, Genetics and Environmental Risk Factors in Schizophrenia) along with the follow up study BMEDS (funded by Brain and Behavior Research Foundation (BBRF), Grant ID: 26985). With BRIDGE-S we aim at building a new cohort with 2500 schizophrenia cases and 2500 controls to contribute to the international project of understanding the fundamental biology of psychiatric disease, especially schizophrenia. With BMEDS we aim to deeply phenotype of individuals with extreme genotype configurations.

We provide support and knowledge in all of the following:

Study preparation and administration

a) Study design, power analyses, literature research, pilot study planning

b) Grant writing

c) Recruitment and biological specimen collection (blood, saliva)

d) Ethics approval

e) Material Transfer Agreement (MTA) preparation and handling.

f) GDPR Compliance — European data protection law effective May 25th 2018

g) Networking with established genetic research institutions.

h) Manuscript preparation, review and submission for publication.

i) Teaching and training in the below analysis methods

In Vitro Analysis

a) DNA extraction (with external collaborators)

b) Chip Genotyping (with external collaborators), currently using the Global Screening Array (GSA chip)

c) Biobank storage

In Silico Analysis

a) Genotype Calling, Copy Number Variant (CNV) Calling

b) Technical Quality Control (QC)

  • Missing rate (SNPs / individuals)
  • Hardy Weinberg Equilibrium (HWE) testing
  • Heterozygosity outlier exclusion
  • Sex checks

c)  Genomic QC

  • Principal Component Analysis (PCA) outlier detection
  • Ancestry mapping
  • Overlap / relatedness testing

d) Alignment to imputation reference panels

e) Phasing

f) Imputation

g) Heritability and confounding estimation via LDScore regression

h) Partitioned heritablity

i) Association analyses

j) Polygenic Risk Scoring (PRS)

k) Functional annotation of variants via FUMA

SNP2GENE analysis

  • SNP annotation
  • Functional gene mapping (Positional, eQTL and chromatin interaction mapping)
  • MAGMA: gene analysis
  • MAGMA: gene set analysis

GENE2FUNC analysis

  • Differentially expressed analysis and tissue specificity
  • Gene set enrichment analysis

l) Transcriptome-wide Association Study (TWAS)

m) Epigenome-wide Association Study (EWAS)

n) Mendelian Randomization

o) Genetic correlation and heritability via LD Hub

p) Simulation analysis

q) Web-based data presentation

r) High Performance Computing (HPC) with access to several Computer Clusters

In Vivo Analysis

a) Re-contacting of subjects for deep phenotyping and precision medicine study designs

b) Collaboration with pharmaceutical companies for early phase trials

GResU is funded by:

1) Berlin Institute of Health (BIH)

2) National Institute of Mental Health (NIMH, PAR-14-165)

3) Stanley Center (Broad Institute)

4) NCRC/NeuroCure

5) Brain and Behavior Research Foundation (BBRF)

6) German Research Foundation (DFG, RI 2846/1-1)

Collaborating groups from the medical research community:

1) Psychiatric Genomics Consortium (PGC)

2) Research Division of Mind and Brain

3) ENIGMA

4) Imagen

5) GAPS

6) GIANT

7) HIV controller

8) IBDGC

9) IntegraMent

10) MooDS

11) FOR 1617

12) NGFN

13) International Consortium on Lithium Genetics (ConLiGen)

14) Furthermore we have direct collaborations with single PIs: