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Interesting GWAS of human ageing based on PCA analysis of multiple ageing phenotypes (mother and father life span, longevity etc.)
https://www.biorxiv.org/content/10.1101/2021.01.22.427837v1
https://www.biorxiv.org/content/10.1101/2021.01.22.427837v1
As I often recommend, here too effect size plot is more informative than P value plot. Some of the large effect gene candidates illustrate nicely what one might find in such a GWAS: genes linked to world's leading causes of death.
According to WHO these are the leading causes of death worldwide. Pretty much anyone can guess the top 1: heart attack
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
The gene SLC22A1 popping out as the largest effect hit is really interesting. It's a major drug metabolizer gene (particularly metformin) and is expressed ONLY in liver.
PheWAS analysis of SLC22A1 points mostly to cardiovascular phenotypes. Most probably this hit is reflecting the leading cause of death worldwide: cardiovascular diseases and perhaps also diabetes.
Second hit ApoE as everone knows is the largest risk factor for Alzheimer's, which is the seventh leading cause of death.
Third hit LPA is again with no doubt points to myocardial infarction. In the recent VNTR UKBB paper, there is a beautiful plot showing the relationship between genetically predicted LpA levels and risk for MI
https://www.biorxiv.org/content/10.1101/2021.01.19.427332v1
https://www.biorxiv.org/content/10.1101/2021.01.19.427332v1
Fourth hit HLA-DRB1 is a master killer being linked with an army of diseases. So there shouldn't be any doubt why this locus is linked to mortality.
https://medlineplus.gov/genetics/gene/hla-drb1/#conditions
https://medlineplus.gov/genetics/gene/hla-drb1/#conditions
Fifth hit is USP28 is involved in DNA damage pathway and linked to several types of cancer. So, probably this hit points to another leading cause of death: cancer. https://www.nature.com/articles/s41419-017-0208-z
One striking observation in this plot is there seems to be no evidence for negative selection for these hits as the allele frequency for most of these hits are large. This is a nice demonstration that they are all linked to late onset diseases and are not under selection.
