Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10⁻⁴). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10⁻⁴). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.

成人身高是人类多基因适应最早的假定例子之一。然而，这一结论最近受到了挑战，因为大规模联合研究中残留的未校正分层被认为是造成之前提到的遗传差异的原因。因此，身高基因座是否在任何人类群体中表现出多基因适应信号仍然是一个悬而未决的问题。我们重新审视了这个问题，除了欧洲大陆人口之外，还重点关注了欧洲人口最矮的国家之一——撒丁岛人。我们利用日本生物银行 (BBJ) 数据集中与身高相关的基因座，进一步缓解了对 GWAS 基因座确定存在偏差的担忧，并表明撒丁岛人在中性条件下仍显着低于预期（比具有北方和北美血统的犹他州居民短约 0.22 个标准差）西欧 [CEU] 基于多基因身高评分，p = 3.89 × 10 ^-4 ）。我们还发现，撒丁岛人口和英国人口之间的多基因身高得分轨迹至少在过去 10,000 年中存在差异 (p = 0.0082)，这与主要由撒丁岛人口驱动的多基因适应特征一致。尽管基于多基因评分的分析显示欧洲大陆人群中存在更微妙的特征，但我们通过使用基于单倍型的统计数据，即由身高驱动的性状单例密度评分（tSDS），在英国人群中发现了清晰而强大的适应性特征-增加等位基因（p = 9.1 × 10 ^-4 ）。总之，通过确定遥远的东亚人群的身高基因座，我们进一步支持了撒丁岛人中与身高相关的基因座的多基因适应的证据。 在欧洲大陆人中，在基于单倍型的分析中检测到了适应性特征，但在基于多基因评分的分析中未检测到。