SardiNIA

SardiNIA Project Meeting, July 15-16, 2013, Ann Arbor, MI

Agenda

Medical Sequencing Project

Focused on the Genetics of Personality and Blood Lipid Levels.

Sardinia: NHGRI Data Release Guidelines

Updates on sequencing project: SardiNIA_sequencing

Ongoing Commitments for Traits analyses and Point Persons

Jennifer Bragg-Gresham

• • MAGIC Gwas of Glucose Changes over time
  • MAGIC GWAS body shape
  • GCLC Metabochip (Lipids)
  • MAGIC Kidney Disease (GWAS unrelated)

Serena Sanna

• • GIANT extreme analysis (GWAS unrelated)
  • MAGIC Metabochip Glucose, Hba1C, Insulin
  • MAGIC Metabochip sex-specific analysis for Glucose, HbA1c, Insulin
  • Analysis of LDL genes sequenced with Sanger and followed up on metabochip.

Serena's team (Italy)

• • Metathyroid: TSH and fT4 meta-analysis
  • Heam GENL PLT -Platelets count
  • CHARGE: PR interval
  • SardiNIA GWAS: hsCRP, MCP-1, Il-6, ESR (cytokines)
  • SardiNIA GWAS: HBF (fetal hemoglobin)
  • MAGIC GLUCOSE based on 1000G imputation
  • Fibrinogen meta-analysis
  • Uric Acid meta-analysis

Osorio Meirelles (NIH)

• • QTGEN metabochip (QT interval)
  • BPGEN metabochip (Blood Pressure traits)
  • NEOPRGEN meta-analysis of personality traits

Paul Scheet (Huston)

• • Vitamin B12, Folate Meta-analysis
  • Meta-analysis of smoking related traits

Miscellaneous Stuff

A nice set of slides on quality control for sequencing projects, generated by Mark Rieder at the University of Washington.

Mark Rieder Quality Control Slides

Imputation and Association Analysis Pipeline

Metabochip

Participants and Available Traits

Sardinia Meeting Notes

Trait Labels

Current Status

There is a preliminary set of ~5,500 individuals with good quality data that we can use for analyses.

Files are on fantasia, with specific paths listed below. Maps are on Build36.3. Alleles are aligned to forward strand

If you have questions, ask Carlo and Serena.

 ## genotypes ped dat and map files
 /share/SardiNIA/metabochip/metabochip.fwstrand.ped.gz
 /share/SardiNIA/metabochip/metabochip.map ---- one dat for each chr ----
 /share/SardiNIA/chr*.freq   ---- one freq for each chr ----

 ## phenotype files, but you could remake if need  different covariates/exclusions and such.
 /home/sannas/metabochip/metabochip_1st_visit.ped
 /home/sannas/metabochip/metabochip_1st_visit.dat

We have also dosages files, so that you can run analysis with merlin-offline and get things much fasters! (20 min for WG instead of 2 hours!)

 ## dosages files.
 /home/sannas/metabochip/dosages/chr*-infer.ped.gz
 /home/sannas/metabochip/dosages/chr*-infer.dat

These files will be moved to share when the new set of genotypes will be integrated.

Methylation

Files

fantasia:/home/hmkang/prj/SardiNIA/methyl
/home/hmkang/prj/SardiNIA/methyl/data/perprobe.res/cg00029931.pheno  - example phenotype data (adjusted for batch effect)
/home/hmkang/prj/SardiNIA/methyl/data/methyl_betas_res_header_paste.txt

Action Items

• mQTL mapping : merlin-offline or emmax
• preparing files : need to extract genotypes for those individuals from VCF
  • VCF file to either merlin or PLINK format - Serena
  • metabochip to either merlin or PLINK format - Serena
  • phenotype file to merlin format (original beta + sex and batch as covariates) Serena
• Identity genes corresponding to the probes with positive heritability. (or 0.3?) - Hyun
• Email to Liming about the sanity of our data (distribution of heritability, normalization, resolution of the association) - Hyun

Information

• 
• Methylation Base Calling Challenges

Key References

If you are looking to learn about the project, I strongly recommend that you read the following papers

Pilia G, Chen WM, Scuteri A, Orru M, Albai G, Dei M, Lai S, Usala G, Lai M, Loi P, Mameli C, Vacca L, Deiana M, Olla N, Masala M, Cao A, Najjar SS, Terracciano A, Nedorezov T, Sharov A, Zonderman AB, Abecasis GR, Costa P, Lakatta E and Schlessinger D (2006). Heritability of Cardiovascular and Personality Traits in 6,148 Sardinians. PLoS Genet 2:1207-1223 [Abstract and PDF]

Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagarajah R, Orru M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder A, Cooper R, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E and Abecasis GR (2007). Genome Wide Association Scan shows Genetic Variants in the FTO gene are Associated with Obesity Related Traits PLoS Genetics 3:1200-10 [Abstract and PDF]