Reduced signal for polygenic adaptation of height in UK Biobank

Berg, Jeremy J; Harpak, Arbel; Sinnott-Armstrong, Nasa; Joergensen, Anja Moltke; Mostafavi, Hakhamanesh; Field, Yair; Boyle, Evan A.; Zhang, Xinjun; Racimo, Fernando; Pritchard, Jonathan K.; Coop, Graham

doi:10.7554/elife.39725

Cited by 353 publications

(451 citation statements)

References 52 publications

Supporting

Mentioning

429

Contrasting

Order By: Relevance

“…These results are consistent with either overcorrection of structure within the UKBB or undercorrection in the GIANT data, although the latter seems more likely based on other recent studies (Berg et al. ; Sohail et al. —see Discussion).…”

Section: Resultssupporting

confidence: 87%

See 1 more Smart Citation

An evolutionary compass for detecting signals of polygenic selection and mutational bias

et al. 2019

View full text Add to dashboard Cite

Selection and mutation shape the genetic variation underlying human traits, but the specific evolutionary mechanisms driving complex trait variation are largely unknown. We developed a statistical method that uses polarized genome‐wide association study (GWAS) summary statistics from a single population to detect signals of mutational bias and selection. We found evidence for nonneutral signals on variation underlying several traits (body mass index [BMI], schizophrenia, Crohn's disease, educational attainment, and height). We then used simulations that incorporate simultaneous negative and positive selection to show that these signals are consistent with mutational bias and shifts in the fitness‐phenotype relationship, but not stabilizing selection or mutational bias alone. We additionally replicate two of our top three signals (BMI and educational attainment) in an external cohort, and show that population stratification may have confounded GWAS summary statistics for height in the GIANT cohort. Our results provide a flexible and powerful framework for evolutionary analysis of complex phenotypes in humans and other species, and offer insights into the evolutionary mechanisms driving variation in human polygenic traits.

show abstract

Section: Resultssupporting

confidence: 87%

“…The nonreplication of height is in concordance with other recent studies finding reduced evidence for selection on height in the UK Biobank cohort applying different methods (Berg et al. ; Sohail et al. ).…”

Section: Discussionsupporting

confidence: 91%

An evolutionary compass for detecting signals of polygenic selection and mutational bias

et al. 2019

View full text Add to dashboard Cite

show abstract

“…As the large effect loci are often the ones detected in FST -outlier tests and forming allele frequency clines, the absence of such loci in this study may not be surprising. Detection of alleles with smaller effect may require considerably larger sample size and different approaches (Berg & Coop, 2014;Field et al, 2016;Racimo, Berg, & Pickrell, 2018), but even when applying such methods it may be challenging to control for population structure to avoid false positive signal (Berg et al, 2019).…”

Section: Putative Signs Of Local Adaptationmentioning

confidence: 99%

“…For instance, allele surfing may occur during a population expansion producing clines in neutral allele frequencies (Klopfstein, Currat, & Excoffier, 2006), or spatial autocorrelation in environmental variables of nearby sampling sites may produce false positive signals in environmental association analysis. Powerful methods for uncovering weaker genomic signals of clinal polygenic adaptation can be used if ample genomic resources and information on phenotypic associations are available (Berg & Coop, 2014;Field et al, 2016), but even in such cases it may be difficult to control for population structure to avoid false positive signal (Berg et al, 2019). Furthermore, convergent adaptation may also complicate the efforts to locate the molecular basis of adaptive variation (Ralph & Coop, 2015).…”

Section: Introductionmentioning

confidence: 99%

Genomics of clinal local adaptation inPinus sylvestrisunder continuous environmental and spatial genetic setting

Tyrmi

Vuosku

Acosta

et al. 2019

Preprint

View full text Add to dashboard Cite

Understanding the consequences of local adaptation at the genomic diversity is a central goal in evolutionary genetics of natural populations. In species with large continuous geographical distributions the phenotypic signal of local adaptation is frequently clear, but the genetic background often remains elusive. We examined the patterns of genetic diversity in Pinus sylvestris, a keystone species in many Eurasian ecosystems with a huge distribution range and decades of forestry research showing that it is locally adapted to the vast range of environmental conditions. Making P. sylvestris an even more attractive subject of local adaptation study, population structure has been shown to be weak previously and in this study. However, little is known about the molecular genetic basis of adaptation, as the massive size of gymnosperm genomes has prevented large scale genomic surveys. We generated a both geographically and genomically extensive dataset using a targeted sequencing approach. By applying divergence-based and landscape genomics methods we found that several coding loci contribute to local adaptation. We also discovered a very large (ca. 300 Mbp) putative inversion with a signal of local adaptation, which to our knowledge is the first such discovery in conifers. Our results call for more detailed analysis of structural variation in relation to genomic basis of local adaptation, emphasize the lack of large effect loci contributing to local adaptation in the coding regions and thus point out to the need for more attention towards multi-locus analysis of polygenic adaptation.

show abstract

“…Human height is controlled by more than 500 loci (Wood et al, ), although recent estimates suggest that this number is probably too high since population structure has not been adequately considered (Berg et al, ; Sohail et al ). We choose the following parameter ranges: 0.001–0.01 for the effect sizes (measured in units of the standard deviation, where in the case of human height 1 SD

\approx

6.5 cm; Turchin et al, ), s around 0.1 (Turchin et al, ), the number of loci affecting the trait l = 200, and mutation rate of about 10 −5 per generation.…”

Section: Modelmentioning

confidence: 99%

Important role of genetic drift in rapid polygenic adaptation

John

Stephan

2020

Ecology and Evolution

View full text Add to dashboard Cite

We analyzed a model to determine the factors that facilitate or limit rapid polygenic adaptation. This model includes population genetic terms of mutation and both directional and stabilizing selection on a highly polygenic trait in a diploid population of finite size. First, we derived the equilibrium distribution of the allele frequencies of the multilocus model by diffusion approximation. This formula describing the equilibrium allele frequencies as a mutation‐selection‐drift balance was examined by computer simulation using parameter values inferred for human height, a well‐studied polygenic trait. Second, assuming that a sudden environmental shift of the fitness optimum occurs while the population is in equilibrium, we analyzed the adaptation of the trait to the new optimum. The speed at which the trait mean approaches the new optimum increases with the equilibrium genetic variance. Thus, large population size and/or large mutation rate may facilitate rapid adaptation. Third, the contribution of an individual locus i to polygenic adaptation depends on the compound parameter γipi0qi0, where γi is the effect size, pi0 the equilibrium frequency of the trait‐increasing allele of this locus, and qi0=1-pi0. Thus, only loci with large values of this parameter contribute coherently to polygenic adaptation. Given that mutation rates are relatively small, this is more likely in large populations, in which the effects of drift are limited.

show abstract

Reduced signal for polygenic adaptation of height in UK Biobank

Cited by 353 publications

References 52 publications

An evolutionary compass for detecting signals of polygenic selection and mutational bias

An evolutionary compass for detecting signals of polygenic selection and mutational bias

Genomics of clinal local adaptation inPinus sylvestrisunder continuous environmental and spatial genetic setting

Important role of genetic drift in rapid polygenic adaptation

Contact Info

Product

Resources

About