Copy number variations play important roles in heredity of common diseases: a novel method to calculate heritability of a polymorphism

拷贝数变异在常见疾病的遗传中起着重要作用:一种计算多态性遗传力的新方法

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Abstract

"Missing heritability" in genome wide association studies, the failure to account for a considerable fraction of heritability by the variants detected, is a current puzzle in human genetics. For solving this puzzle the involvement of genetic variants like rare single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) has been proposed. Many papers have published estimating the heritability of sets of polymorphisms, however, there has been no paper discussing the estimation of a heritability of a single polymorphism. Here I show a simple but rational method to calculate heritability of an individual polymorphism, hp(2). Using this method, I carried out a trial calculation of hp(2) of CNVs and SNPs using published data. It turned out that hp(2) of some CNVs is quite large. Noteworthy examples were that about 25% of the heritability of type 2 diabetes mellitus and about 15% of the heritability of schizophrenia could be accounted for by one CNV and by four CNVs, respectively. The results suggest that a large part of missing heritability could be accounted for by re-evaluating the CNVs which have been already found and by searching novel CNVs with large hp(2).

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