Pathway-based genome-wide association studies reveal that the Rac1 pathway is associated with plasma adiponectin levels

Wei Dong Li, Hongxiao Jiao, Kai Wang, Fuhua Yang, Struan F.A. Grant, Hakon Hakonarson, Rexford Ahima, R. Arlen Price

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Pathway-based analysis as an alternative and effective approach to identify disease-related genes or loci has been verified. To decipher the genetic background of plasma adiponectin levels, we performed genome wide pathway-based association studies in extremely obese individuals and normal-weight controls. The modified Gene Set Enrichment Algorithm (GSEA) was used to perform the pathway-based analyses (the GenGen Program) in 746 European American females, which were collected from our previous GWAS in extremely obese (BMI>35kg/m 2) and never-overweight (BMI<25kg/m 2) controls. Rac1 cell motility signaling pathway was associated with plasma adiponectin after false-discovery rate (FDR) correction (empirical P<0.001, FDR=0.008, family-wise error rate=0.008). Other several Rac1-centered pathways, such as cdc42racPathway (empirical P<0.001), hsa00603 (empirical P=0.003) were among the top associations. The RAC1 pathway association was replicated by the ICSNPathway method, yielded a FDR=0.002. Quantitative pathway analyses yielded similar results (empirical P=0.001) for the Rac1 pathway, although it failed to pass the multiple test correction (FDR=0.11). We further replicated our pathway associations in the ADIPOGen Consortium data by the GSA-SNP method. Our results suggest that Rac1 and related cell motility pathways might be associated with plasma adiponectin levels and biological functions of adiponectin.

Original languageEnglish (US)
Article number13422
JournalScientific reports
StatePublished - Aug 24 2015
Externally publishedYes

ASJC Scopus subject areas

  • General


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