Further dissection and application of disappearing heritability

1,开局一张图

下面的NatureA picture posted above：https://www.nature.com/news/2008/081105/pdf/456018a.pdf

消失的遗传力,Like the disappearing bullet in a suspense movie,Scientists are detectives,通过各种工具（生物统计、生物信息、数量遗传、基因测序）Let's find out where the lost heredity has gone.

所以,The image of a scientist is like this：

If we find the missing heritability,Find out why it disappeared and how to find it,The pay is huge：

2,丢失的遗传力

“遗传力丢失”（ Missing heritability）是一个重要的数量遗传学问题,即通过遗传标记estimated heritability以及通过全基因组关联分析（GWAS）发现的所有相关基因所贡献的遗传力总和均低于实际的遗传力.

举个栗子：

比如,If the heritability of height is0.8,但是GWAS分析中显著性的SNP只解释了45%的变异（遗传力为0.45）,这样还是有0.35的遗传力丢失了,这就叫做丢失的遗传力.

3,Further dissection of vanishing heritability

参考：

Witte JS, Visscher PM, Wray NR. The contribution of genetic variants to disease depends on the ruler. Nat Rev Genet. 2014 Nov;15(11):765-76. doi: 10.1038/nrg3786. Epub 2014 Sep 16. PMID: 25223781; PMCID: PMC4412738.

Genetic breakdown：

• Total heritability,is the actual heritability,Mainly from family groups（such as identical twins、全同胞）estimated heritability,对应的是family遗传力

• Chip heritability,是通过REMLestimated heritability,All are usedSNP数据,比如GCTA、asreml中的GBLUP,The estimated heritability falls into this category,对应的是SNP遗传力

• Heritability due to known variants,是GWASsignificant in the analysisSNPestimated heritability,对应的是PVE（Explain the percentage）,对应的是GWAS遗传力

Generally we think that the heritability of disappearance is ：

$$h_{family}^2-h_{GWAS}^2$$

But it can be further divided into two parts：

• 第一部分：Still-missing heritability,It's hereditary that is still missing,它的计算公式是$h_{family}^2-h_{SNP}^2$,它的来源是GWASUncatchable variation,比如CNV,SV等,by adding sources of variation（CNV,SV,PVA）,Rare mutation to solve.（Pan-genome application range）

• 第二部分：Hiding heritability,It's a hidden heritability,它的计算公式是$h_{SNP}^2-h_{GWAS}^2$,It is mainly due to the fact that some sites with small effects are not detected by current statistical methods（假阴性）,The value of this part can be reduced by the sample size.

4, How to harness the missing heritability

育种中,The level of heritability is directly related to how it is applied and the quality of selection.

such as heredity0.9100-grain weight,No molecular markers are used,No genealogy,不用GS,Direct phenotype selection will do,这才是真正的：

老子英雄儿好汉……

Moderate heritability,You need the help of half-sibs、全同胞,With the help of family、The pedigree is selected

低遗传力,就需要借助MAS和GS进行选择了

And if the heritability of a trait,Decreased vanishing heritability,Yes the operational part has been added,Then the accuracy of the estimation will be improved,Increase the selection accordingly,Increased selection efficiency.

因此,Improve the efficiency of breeding selection,可以从两个方面：

第一个方面,降低“依旧消失的遗传力”,The specific performance is to find a variety of sources of variation,such as pan-genomes、Graph pan-genomes to find more accurate variants（SV,Indel）,This method can be used in MAS,也可以用在GS上.

第二个方面,降低“隐藏的遗传力”,The specific performance is to increase the sample size,GSin expanding the number of reference groups,GWASincrease the number of samples,增大SNPVariation sites, etc.

One view of the three bodies is“lock technology”,He believes that the development of science and technology comes from the mastery and control of microscopic matter,Quantum physics that locks humans,No further gene editing can be performed、Atomic energy utilization、星际飞船、Human brain computer and other fields.

同样的道理,for heritability,We further dissect the vanishing heritability,找到对应的解决方案（such as adding sources of variation,增大样本量）,就有了方向,Targeted improvement and resolution.

This is the scientific way of solving problems！