All of these studies have been based on SNP associations, in most cases with 81 effect sizes discovered by the GIANT Consortium, which most recently combined 79 82 individual GWAS through meta--analysis, encompassing a total of 253,288 83 individuals. [13,14] Here, we show that the selection effects described in these 84 studies are severely attenuated and in some cases no longer significant when using 85 summary statistics derived from the UK Biobank, an independent and larger single 86 study that includes 336,474 genetically unrelated individuals who derive their 87 ancestry almost entirely from British Isles (identified as "white British ancestry" by 88 the UK Biobank) (Supplementary Table S1). The UK Biobank analysis is based on a 89 single cohort drawn from a relatively homogeneous population enabling excellent 90 control of potential population stratification. Our analysis of the UK Biobank data 91 confirms that almost all genome--wide significant loci discovered by the GIANT 92 We began by estimating "polygenic height scores"-sums of allele 101 frequencies at independent SNPs from GIANT weighted by their effect sizes-to 102 study population level differences among ancient and present--day European 103 samples. We used a set of different significance thresholds and strategies to correct 104 for linkage disequilibrium as employed by previous studies, and replicated their 105 signals for significant differences in genetic height across populations. [4-11] 106 ( Figure 1a, Supplementary Figure S2). We then repeated the analysis using 107 summary statistics from a GWAS for height in the UK Biobank restricting to 108 individuals of British Isles ancestry and correcting for population stratification 109 based on the first ten principal components (UKB).ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . http://dx.doi.org/10.1101/355057 doi: bioRxiv preprint first posted online Jun. 25, 2018[15] This analysis resulted in a 110 dramatic attenuation of differences in polygenic height scores (Figure 1a, 111Supplementary Figures S2--S4). The differences between ancient European 112 populations also greatly attenuated (Figure 1a, Supplementary Figure S5). 113 Strikingly, the ordering of the scores for populations also changed depending on 114 which GWAS was used to estimate genetic height both within Europe (Figure 1a, 115 Supplementary Figures S2--S5) and globally (Supplementary Figure S6), 116 consistent with reports from a recent simulation study.[16] The height scores were 117 qualitatively similar only when we restricted to independent genome--wide 118 significant SNPs in GIANT and the UK Biobank (P < 5x10 --8 ) (Supplementary Figure 119 S2b). This replicates the originally reported significant north--south difference in the 120 allele frequency of the height--increasing allele [4] Figure S2b), and that confounding due to stratificat...

Editing of plastid RNAs proceeds by C-to-U, in hornwort species also by extensive U-to-C, transitions, which predominantly lead to the restoration of codons for structurally and/or functionally important, conserved amino acid residues. So far, only one instance of editing outside coding regions has been reported - in the psbL/ psbF intergenic region of Ginkgo biloba. This site was proposed to have no functional importance. Here we present an evaluation of an editing site in the ndhI/ ndhG intergenic region in a related group of monocot plants. Efficient editing of this site, as well as the phylogenetic conservation of the resulting uridine residue, point at an important role for the sequence restored by editing. Two potential functions can be envisaged. (1) RNA secondary structure predictions suggest that the C-to-U conversion at this site can lead to a modified stem/loop structure of the ndhG 5' UTR, which could influence ndhG expression. (2) Alternatively, editing of the ndhI/ ndhG intergenic region may tag a so far unidentified small (12-codon) ORF, and lead to the restoration of a conserved phenylalanine codon. A screen with specific antibodies elicited against the putative peptide failed to detect such a peptide in chloroplast fractions. However, this failure may be attributable to its low and/or development-specific expression.

The genetic architecture of most human complex traits is highly polygenic, motivating efforts to detect polygenic selection involving a large number of loci. In contrast to previous work relying on top GWAS loci, we developed a method that uses genome-wide association statistics and linkage disequilibrium patterns to estimate the genome-wide genetic component of population differentiation of a complex trait along a continuous gradient, enabling powerful inference of polygenic selection. We analyzed 43 UK Biobank traits and focused on PC1 and North-South and East-West birth coordinates across 337K unrelated British-ancestry samples, for which our method produced close to unbiased estimates of genetic components of population differentiation and high power to detect polygenic selection in simulations across different trait architectures. For PC1, we identified signals of polygenic selection for height (74.5±16.7% of 9.3% total correlation with PC1 attributable to genome-wide genetic effects; P = 8.4×10-6 ) and red hair pigmentation (95.9±24.7% of total correlation with PC1 attributable to genome-wide genetic effects; P = 1.1×10 -4 ); the bulk of the signal remained when removing genomewide significant loci, even though red hair pigmentation includes loci of large effect. We also detected polygenic selection for height, systolic blood pressure, BMI and basal metabolic rate along North-South birth coordinate, and height and systolic blood pressure along East-West birth coordinate. Our method detects polygenic selection in modern human populations with very subtle population structure and elucidates the relative contributions of genetic and non-genetic components of trait population differences.

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