Wednesday, October 28, 2015

Genetic group differences in height and recent human evolution

These recent Nature Genetics papers offer more evidence that group differences in a complex polygenic trait (height), governed by thousands of causal variants, can arise over a relatively short time (~ 10k years) as a result of natural selection (differential response to varying local conditions). One can reach this conclusion well before most of the causal variants have been accounted for, because the frequency differences are found across almost all variants (natural selection affects all of them). Note the first sentence above contradicts many silly things (drift over selection, genetic uniformity of all human subpopulations due to insufficient time for selection, etc.) asserted by supposed experts on evolution, genetics, human biology, etc. over the last 50+ years. The science of human evolution has progressed remarkably in just the last 5 years, thanks mainly to advances in genomic technology.

Cognitive ability is similar to height in many respects, so this type of analysis should be possible in the near future.

See discussion in earlier posts:
Height, breeding values and selection
Recent human evolution: European height
Eight thousand years of natural selection in Europe
No genomic dark matter
Population genetic differentiation of height and body mass index across Europe

Nature Genetics 47, 1357–1362 (2015) doi:10.1038/ng.3401

Across-nation differences in the mean values for complex traits are common1, 2, 3, 4, 5, 6, 7, 8, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10−8; BMI, P < 5.95 × 10−4), and we find an among-population genetic correlation for tall and slender individuals (r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).

Height-reducing variants and selection for short stature in Sardinia

Nature Genetics 47, 1352–1356 (2015) doi:10.1038/ng.3403 
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.

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