Thursday, September 10, 2020

Rare Variants For Human Height

At left, genetics of height. By The original uploader was Pete.Hurd at English Wikipedia - Transferred from en.wikipedia to Commons by MichaelSchoenitzer using CommonsHelper., Public Domain, 
https://commons.wikimedia.org/w/index.php?curid=19496489

Interesting paper, abstract:

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Obviously, there's nothing you can do about what gene variants you inherited and nothing you can do about height as an adult, but genetic height potential can be maximized by having adequate nutrition while growing, which is why people in given populations tend to be taller today than in centuries past.

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