Dražen Pulanić, Ozren Polašek, Mladen Petrovečki, Ariana Vorko-Jović, Marijana Peričić, Lovorka Barać Lauc, Irena Martinović Klarić, Zrinka Biloglav, Ivana Kolčić, Lina Zgaga, Andrew D. Carothers, Senad Ramić, Mia Šetić, Branka Janićijević, Nina Smolej Narančić, Kajo Bućan, Diana Rudan, Gordon Lowe, Ann Rumley, Pavao Rudan, Harry Campbell, Igor Rudan
Human Biology 80 (5), 513-533, (1 October 2008) https://doi.org/10.3378/1534-6617-80.5.513
KEYWORDS: HEMOSTASIS, Inflammation, isolation, inbreeding, heterosis, individual genome-wide heterozygosity, multilocus heterozy-gosity, fibrinogen, D-dimer (Dd), von Willebrand Factor (vWF), tissue plasminogen activator (tPA), C-reactive protein (CRP), cardiovascular risk, Croatia
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.