Human Molecular Genetics Advance Access originally published online on January 12, 2007
Human Molecular Genetics 2007 16(2):233-241; doi:10.1093/hmg/ddl473
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Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits
1 Department of Public Health Sciences, University of Edinburgh, Edinburgh, UK, 2 MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK, 3 School of Public Health, University Medical School, Zagreb, Croatia, 4 Institute of Anthropological Research, Zagreb, Croatia and 5 Molecular Diagnostic Genotyping Laboratory, Marshfield Clinic Research Foundation, Marshfield, USA
* To whom correspondence should be addressed at: Department of Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, Scotland EH8 9AG, UK. Tel: +44 1316506984; Fax: +44 1316506909; Email: harry.campbell{at}ed.ac.uk
Received August 20, 2006; Accepted December 17, 2006
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, hR, 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 hR, 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 hR 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 hR 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.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.