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Effects of isolation and inbreeding on human quantitative traits: an example of biochemical markers of hemostasis and inflammation

Research output: Contribution to journalArticle

  • Drazen Pulanić
  • Ozren Polasek
  • Mladen Petrovecki
  • Ariana Vorko-Jović
  • Marijana Pericić
  • Lovorka Barać Lauc
  • Irena Martinović Klarić
  • Zrinka Biloglav
  • Ivana Kolcić
  • Andrew D Carothers
  • Senad Ramić
  • Mia Setić
  • Branka Janićijević
  • Nina Smolej Narancić
  • Kajo Bućan
  • Diana Rudan
  • Gordon Lowe
  • Ann Rumley
  • Pavao Rudan

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)513-33
Number of pages21
JournalHuman Biology
Issue number5
Publication statusPublished - 2008


Isolation is a known force in evolutionary biology and one of the main factors in speciation. One of the main consequences of severe isolation is reduced mate choice, which results in the occurrence of inbreeding as a result of isolation. We investigated the effects of individual genome-wide heterozygosity measured as the multilocus heterozygosity (MLH) on biochemical markers of hemostasis and inflammation in 1,041 individuals from the island of Vis, Croatia, where inbreeding is prevalent and a wide range of variation in the genome-wide heterozygosity is expected. Assessment of individual genome-wide heterozygosity was based on genome-wide scans using 800 microsatellite (STR) and 317,503 single nucleotide (SNP) polymorphic markers in each examinee. In addition, for each examinee we defined a personal genetic history (PGH) based on genealogical records. The association between PGH and MLH and fibrinogen, D-dimer (Dd), von Willebrand factor (vWF), tissue plasminogen activator (tPA), and C-reactive protein (CRP) was performed with a mixed model, controlling for possible confounding effects. PGH was a significant predictor only for tPA (P <0.001), whereas neither of the two MLH measures exhibited significant association with any of the investigated traits. The effects of individual genome-wide heterozygosity are most likely expressed in highly polygenically determined traits or in traits that are mediated by rare and recessive genetic variants. Weak associations between PGH and MLH and markers of hemostasis and inflammation suggest that their genetic control may not be highly polygenic and that they could be promising targets for genetic association studies.

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