Lack of statistical power as a major limitation in understanding MHC-mediated immunocompetence in wild vertebrate populations

Disentangling the sources of variation in developing an effective immune response against pathogens is of major interest to immunoecology and evolutionary biology. To date, the link between immunocompetence and genetic variation at the major histocompatibility complex (MHC) has received little attention in wild animals, despite the key role of MHC genes in activating the adaptive immune system. Although several studies point to a link between MHC and immunocompetence, negative findings have also been reported. Such disparate findings suggest that limited statistical power might be affecting studies on this topic, owing to insufficient sample sizes and/or a generally small effect of MHC on the immunocompetence of wild vertebrates. To clarify this issue, we investigated the link between MHC variation and seven immunocompetence proxies in a large sample of barn owls and estimated the effect sizes and statistical power of this and published studies on this topic. We found that MHC poorly explained variation in immunocompetence of barn owls, with small-to-moderate associations between MHC and immunocompetence in owls (effect size: 0.1≥r≤0.3) similar to other vertebrates studied to date. Such small-to-moderate effects were largely associated with insufficient power, which was only sufficient (>0.8) to detect moderate-to-large effect sizes (r≥0.3). Thus, studies linking MHC variation with immunocompetence in wild populations are underpowered to detect MHC effects, which are likely to be of generally small magnitude. Larger sample sizes (>200) will be required to achieve sufficient power in future studies aiming to robustly test for a link between MHC variation and immunocompetence.

解析宿主针对病原体产生有效免疫应答的变异来源，是免疫生态学与进化生物学领域的核心研究议题之一。尽管主要组织相容性复合体（major histocompatibility complex, MHC）基因在激活适应性免疫系统中发挥关键作用，但迄今为止，野生脊椎动物中免疫能力与MHC遗传变异之间的关联却鲜有研究关注。尽管已有部分研究指出MHC与免疫能力之间存在关联，但也有不少研究得出了阴性结果。这类不一致的研究结果提示，由于样本量不足，以及MHC对野生脊椎动物免疫能力的效应量普遍较小，该领域的相关研究可能存在统计效力不足的问题。为厘清这一问题，本研究以大样本仓鸮群体为研究对象，分析了MHC变异与7项免疫能力替代指标之间的关联，并估算了本研究及已发表的同类研究的效应量与统计效力。研究结果显示，MHC对仓鸮免疫能力变异的解释度极低；仓鸮体内MHC与免疫能力之间的关联强度处于小到中等水平（效应量：0.1≥r≤0.3），与迄今已研究的其他脊椎动物结果一致。这类小到中等强度的效应量大多与统计效力不足相关：只有当效应量达到中等到较大水平（r≥0.3）时，研究的统计效力才足以检出该关联（效力>0.8）。因此，在野生种群中开展MHC变异与免疫能力关联研究的现有文献，其统计效力均不足以检出MHC的效应——而这类效应本身大概率普遍较弱。未来若要稳健检验MHC变异与免疫能力之间的关联，需采用更大的样本量（>200）以获得足够的统计效力。