title: Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits.
abstract: The dramatic changes in human population structure over the last 200 years have resulted in significant levels of outbreeding, which, in turn, is predicted to lead to increased levels of individual genetic diversity (genome-wide heterozygosity, h). To investigate possible effects of these large demographic changes on global health, we studied the effect of h, measured as relative heterozygosity, h(R), on 15 disease-related traits in four groups of individuals with widely differing ancestral histories (ranging from outbred to inbred) from the Dalmatian islands in Croatia. Higher levels of h(R), estimated using 1184 STR/indel markers, were found in the outbred group (P < 0.0001) and were associated with lower blood pressure (BP) and total/LDL cholesterol (P = 0.01 and 0.01, respectively) after controlling for other factors, with BP showing a strong sex effect (males P > 0.5 and females P = 0.002). These findings, if replicated, suggest that h(R) be considered as a genetic risk factor in genetic epidemiological studies on common disease traits. They are consistent with the well-known effects of heterosis (hybrid vigour) described when outcrossing animals and plants. Outbreeding resulting from urbanization and migration from traditional population subgroups may be leading to increasing h(R) and may have beneficial effects on a range of traits associated with human health and disease. Other traits, such as age at menarche, IQ and lifespan, which have been changing during the decades of urbanization, may also have been influenced by demographic factors.
authors.affiliation: Department of Public Health Sciences, University of Edinburgh, Edinburgh, UK. harry.campbell@ed.ac.uk
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Carothers
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Biloglav
authors.forename: Lovorka
authors.initials: L
authors.lastname: Barac
authors.forename: Marijana
authors.initials: M
authors.lastname: Pericic
authors.forename: Branka
authors.initials: B
authors.lastname: Janicijevic
authors.forename: Nina
authors.initials: N
authors.lastname: Smolej-Narancic
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcic
authors.forename: James L
authors.initials: JL
authors.lastname: Weber
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.forename: Pavao
authors.initials: P
authors.lastname: Rudan
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
mesh_terms: D000367:Age Factors; D001794:Blood Pressure; D001827:Body Height; D008078:Cholesterol, LDL / Q000097:blood; D017523:Croatia; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D005828:Genetics, Population; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D019655:Quantitative Trait, Heritable; D012737:Sex Factors; D012959:Socioeconomic Factors
chemical_list: D008078:Cholesterol, LDL; D005819:Genetic Markers