Background: Although numerous genes are known to regulate serum lipid traits, identified variants explain only a small proportion of the expected heritability. Objects: We intended to identify further genetic variants associated with lipid phenotypes in a self-contained population of Sorbs in Germany. Material and Methods: We performed a genome wide association study (GWAS) on LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride levels (TG) in 839 Sorbs. All single nucleotide polymorphisms (SNPs) with a P-value < 0.01 were taken forward to a meta-analysis including an independent Swedish cohort (Diabetes Genetics Initiative [DGI]; n~3100). Novel association signals with the strongest effects were taken forward to replication studies in an additional German cohort (Berlin, n=2031). Results: In the initial GWAS in the Sorbs we identified 14 loci associated with lipid phenotypes reaching P values < 10(-5) and confirmed significant effects for 18 previously reported loci. The combined meta-analysis of the three study cohorts (n(HDL) =6041, n(LDL)=5995, n(TG)=6087) revealed a novel association for a variant in THOC5 (rs8135828) with serum HDL-C levels (P=1.78x10(-7), Z-Score = 5.221). Consistently, the variant was also associated with circulating APOA1 levels in Sorbs. The siRNA mediated mRNA silencing of THOC5 in HepG2 cells resulted in lower mRNA levels of APOA1, SCARB1 and ABCG8 (all P<0.05). Conclusion: We propose THOC5 to be a novel gene involved in the regulation of serum HDL-C levels.