TY - JOUR
T1 - Partial correlation network analyses to detect altered gene interactions in human disease
T2 - Using preeclampsia as a model
AU - Johansson, Åsa
AU - Løset, Mari
AU - Mundal, Siv B.
AU - Johnson, Matthew P.
AU - Freed, Katy A.
AU - Fenstad, Mona H.
AU - Moses, Eric K.
AU - Austgulen, Rigmor
AU - Blangero, John
N1 - Funding Information:
Acknowledgments This study was supported by grants from FUGE—Functional genomics in Norway within the Research Council of Norway (Åsa Johnasson) and motility grants from NTNU—The Norwegian University of Science and Technology (Åsa Johansson) and Sven och Dagmar Saléns stiftelse (Åsa Johansson). Statistical analysis was supported in part by NIH grant MH59490 (Blangero).
PY - 2011/1
Y1 - 2011/1
N2 - Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value ≤ 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value ≤ 0.05), of which 31 were also significantly different (FDR p value ≤ 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease.
AB - Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value ≤ 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value ≤ 0.05), of which 31 were also significantly different (FDR p value ≤ 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease.
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U2 - 10.1007/s00439-010-0893-5
DO - 10.1007/s00439-010-0893-5
M3 - Article
C2 - 20931231
AN - SCOPUS:78651247734
VL - 129
SP - 25
EP - 34
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 1
ER -