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Trends Genet. 2003 Feb;19(2):97-106.

A polygenic basis for late-onset disease.

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  • 1MRC Human Genetics Unit, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK.


The biological basis of late-onset disease has been shaped by genetic factors subject to varying degrees of evolutionary constraint. Late-onset traits are not only more sensitive to environmental variation, owing to the breakdown of homeostatic mechanisms, but they also show higher levels of genetic variation than traits directly influencing reproductive fitness. The origin and nature of this variation suggests that current strategies are poorly suited to identifying genes involved in many complex diseases.

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