Human Genetics

, Volume 120, Issue 3, pp 360–370 | Cite as

Heterogeneity-based genome search meta-analysis for preeclampsia

  • Elias Zintzaras
  • Georgios Kitsios
  • Gavan A. Harrison
  • Hannele Laivuori
  • Katja Kivinen
  • Juha Kere
  • Ioannis Messinis
  • Ioannis Stefanidis
  • John P. A. Ioannidis
Original Investigation


Preeclampsia is a pregnancy-related disorder that causes maternal and fetal morbidity and mortality. Its exact inheritance pattern is still unknown, and genome searches for identifying susceptibility loci for preeclampsia have thus far produced inconclusive or inconsistent results. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) that synthesized the available genome scan data on preeclampsia. HEGESMA identifies genetic regions (bins) that rank highly on average in terms of linkage statistics across genome scans (searches). The significance of each bin’s average rank and heterogeneity across scans was calculated using Monte Carlo tests. The meta-analysis involved four genome-scans on general preeclampsia and five scans on severe preeclampsia. In general preeclampsia, 13 bins had significantly high average rank (P rank < 0.05) by either unweighted or weighted analyses, while four of them (2p11.2–2q21.1, 9q21.32–9q31.2, 2p15–2p11.2, 2q32.1–2q35) were formally significant by both analyses. Heterogeneity of bin 2.8 (2q32.1–2q35) was significantly low in both unweighted and weighted analysis (P Q  < 0.01). In severe preeclampsia, 10 bins had significantly high average rank by either unweighted or weighted analyses and five of them (3q11.1–3q21.2, 2q37.1–2q37.3, 18p11.32–18p11.22, 2p15–2p11.2, 7q34–7q36.3) were significant by both analyses. Bin 2q37.1–2q37.3 showed marginal low heterogeneity in unweighted and weighted analysis (P Q  = 0.06). Results should be interpreted with caution as the p values were modest. Further investigation of these regions by genotyping with additional markers and families may help to direct the identification of candidate genes for preeclampsia.


Preeclampsia Average Rank Weighted Analysis Genome Scan HELLP Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Elias Zintzaras
    • 1
  • Georgios Kitsios
    • 1
  • Gavan A. Harrison
    • 2
  • Hannele Laivuori
    • 3
    • 4
  • Katja Kivinen
    • 5
  • Juha Kere
    • 5
    • 3
  • Ioannis Messinis
    • 6
  • Ioannis Stefanidis
    • 7
  • John P. A. Ioannidis
    • 8
    • 9
  1. 1.Department of BiomathematicsUniversity of Thessaly School of MedicineLarissaGreece
  2. 2.Division of Environmental and Life SciencesMacquarie UniversityMacquarieAustralia
  3. 3.Department of Medical GeneticsUniversity of HelsinkiHelsinkiFinland
  4. 4.Department of Clinical Genetics, HUSLABUniversity of HelsinkiHelsinkiFinland
  5. 5.Department of Biosciences at NovumKarolinska InstituteHuddingeSweden
  6. 6.Department of Obstetrics and GynaecologyUniversity of Thessaly School of MedicineLarissaGreece
  7. 7.Department of NephrologyUniversity of Thessaly School of Medicine LarissaGreece
  8. 8.Department of Hygiene and EpidemiologyUniversity of Ioannina School of MedicineIoanninaGreece
  9. 9.Department of MedicineTufts University School of MedicineBostonUSA

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