GWAS Analysis of Chromosome 10

(Continuous Variable)Group 5

Hepatic Steatosis: accumulation of triglycerides in hepatocyte lipid droplets

J C Cohen et al. Science 2011;332:1519-1523

LiverTriglycerides

• LiverTGsaremaintainedthrough:• Acquisitionthroughuptakeoflipoproteinparticlesorfreefattyacids(secretedfromwhiteadipose)

• Denovosynthesisfromacetyl-CoAprecursors• Removalviaβ-oxidation,orsecretionofTG-richVLDLparticles

Why Chromosome 10? Significantly differentially expressed gene H2YAF2, from the binary DEG analysis, is located on chromosome 10

Original data = 27658 SNPs

Filtered data = 27339 SNPs

Did NOT filter based on relatedness

Would result in filtering out 15% of SNPs

ZERO genes met the p<10-8 criteriaMost significant gene: p<10-5

TheAlleleFREquency Database(ALFRED)

SNP11010552isinaSNPcluster:Theyareallintergenicb/wLOC439954andPBEF2,allunknownfunctions(frombothUCSCGenomebrowser,GTEx,andALFRED)withsamefrequency

rs7092191(AtoC,r2=.9)rs10827617(AtoC,r2=.632)rs7067812(AtoC,r2=.632)

Next most significant genes: p<10-4

GG AAAG

From:GTEX

*Involvedinfattyacidoxidation(Reactome)eQTL

PHYHexpressionisdiminishedinthepresenceofrs7916990

LiverMuscle

(GTEx)

UCSCGenomeBrowser

rs7916990(neartranscriptionfactorbindingsites)

GTEX(showingeQTL’s forPHYH)

(SNAP)

Thank you!