Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits

被引:84
作者
Campbell, Harry
Carothers, Andrew D.
Rudan, Igor
Hayward, Caroline
Biloglav, Zrinka
Barac, Lovorka
Pericic, Marijana
Janicijevic, Branka
Smolej-Narancic, Nina
Polasek, Ozren
Kolcic, Ivana
Weber, James L.
Hastie, Nicholas D.
Rudan, Pavao
Wright, Alan F.
机构
[1] Univ Edinburgh, Dept Publ Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland
[2] Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
[3] Univ Zagreb, Sch Med, Sch Publ Hlth, Zagreb 41001, Croatia
[4] Inst Anthropol Res, Zagreb, Croatia
[5] Marshfield Clin Fdn Med Res & Educ, Mol Diagnost Genotyping Lab, Marshfield, WI 54449 USA
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1093/hmg/ddl473
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:233 / 241
页数:9
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