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

Pulanić, Dražen and Polašek, Ozren and Petrovečki, Mladen and Vorko-Jović, Ariana and Peričić, Marijana and Barać Lauc, Lovorka and Martinović Klarić, Irena and Biloglav, Zrinka and Kolčić, Ivana and Zgaga, Lina and Carothers, Andrew D. and Ramić, Senad and Šetić, Mia and Janićijević, Branka and Smolej Narančić, Nina and Bučan, Kajo and Rudan, Diana and Lowe, Gordon and Rumley, Ann and Rudan, Pavao and Campbell, Harry and Rudan, Igor (2008) Effects of isolation and inbreeding on human quantitative traits: an example of biochemical markers of hemostasis and inflammation. Human biology, 80 (5). pp. 513-533. ISSN 0018-7143 (Print), 1534-6617 (Online)

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Abstract

Genome-wide multilocus heterozygosity (MLH) can have considerable effects on biological quantitative traits, especially those that are highly polygenically determined or mediated by rare genetic variants. We investigated the effects of MLH on biochemical markers of hemostasis and inflammation in 1, 041 individuals from the island of Vis, Croatia, where consanguinity is prevalent and there is a wide range of MLH values in the population. Assessment of MLH was based on genome-wide scans using 800 microsatellite (STR) and 317, 000 single nucleotide (SNP) polymorphic markers in each examinee. Additionally, for each individual we defined ?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 (t-PA) and C-reactive protein (CRP) was performed with multiple linear regression, while controlling for possible confounding effects. PGH was a significant predictor only for tPA (P<0.001), while neither of the two MLH measures exhibited significant association with any of the investigated traits. Fib was mainly predicted by age and body mass index (P<0.001) ; Dd and vWF by age (P<0.001) and albumin (P=0.004) ; tPA by age, gender, body mass index and triglycerides (P<0.001) ; and CRP by gender, body mass index, albumin and forced expiratory volume in the 1st second (P<0.001). 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 represent promising targets for genetic association studies.

Item Type: Article
Additional Information: Language: English.
Uncontrolled Keywords: Hemostasis, inflammation, isolation, inbreeding, heterosis, individual genome-wide heterozygosity, multilocus heterozygosity, fibrinogen, D-dimer (Dd), von Willebrand factor (vWF), tissue plasminogen activator (tPA), C-reactive protein (CRP), cardiovascular risk, Croatia
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Depositing User: Karolina
Date Deposited: 02 Oct 2015 13:02
Last Modified: 19 Jan 2017 09:02
URI: http://idiprints.knjiznica.idi.hr/id/eprint/372

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