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Wednesday, October 28, 2015

Sardinians: relatively short by design

Behind a pay wall at Nature Genetics:

We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (−0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (−0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.

Zoledziewska et al., Height-reducing variants and selection for short stature in Sardinia, Nature Genetics 47, 1352–1356 (2015) doi:10.1038/ng.3403

Also at Nature Genetics...

We report ~17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ~76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population.

Sidore et al., Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers, Nature Genetics 47, 1272–1281 (2015) doi:10.1038/ng.3368


Simon_W said...

Compare the average statures in Italy around 1860 according to the data gathered by Livi (in cm):

Body height is probably one of the most strongly environment- and nutrition determined characters, and also susceptible to epigenetic effects, so the detection of the "genetic height" is of some importance.

Romulus said...

Would be interesting to see if those height reducing snps were present in the EEF samples.

Karl_K said...

Interesting... As longevity is strongly correlated to shortness, I guess all those secrets to living long by eating like a Sardinian are actually just about genetics, not a Mediterranean diet.

Karl_K said...


That probably goes for the Japanese as well, wouldn't you think?

So why do mammals get smaller on islands, but reptiles get bigger?

bellbeakerblogger said...

"Short Genes"

OMG! I haven't even had a drink yet!

Grey said...

dwarf giants

"So why do mammals get smaller on islands, but reptiles get bigger?"

Interesting question.

Krefter said...

"Would be interesting to see if those height reducing snps were present in the EEF samples."

They are in Neolithic Spain. Sardinians are probably mostly Cardial descended like Neolithic Spanish.

nanuk said...

The title of this post is misleading.

That reaserch published by Nature Genetics included only aged people from three remote villages from Ogliastra (the study was done by the AKEA and University of Sassari which study centenarians living in Sardegna).

The fact that in a group of individuals from 3 villages of Ogliastra was found a gene supposed to reduce of few centimenters the stature compared to the average of the same ethnicity (Sardineans) doesn't mean that sardineans are shorts.

Recent anthropometric surveys show the contrary, Sardineans show an impressive increase in stature, after endemic diseases like malaria weren't eradicated half century ago.

In addition how can you explain that today young sardiniens are much taller than older people, and their life expectancy is higher than in past?