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

Abstract

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: .1 ≥ r ≤ .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 ≥ .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.

Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate

“…Parasite-specific immune responses driven by MHC polymorphisms is extensively supported [57][58][59][60], however in our study we found no evidence of an association between MHC diversity and AdV or helminth infection status. The latter may be the consequence of a lack of statistical power [61] and/or the fact that we are analysing infection status without accounting for specific strains or infection intensity. Another possible caveat in association studies is the use of supertypes to cluster alleles based on functional properties, as done here with the MHCI of mouse lemurs.…”

Borrelia Infection in Bank Voles Myodes glareolus Is Associated With Specific DQB Haplotypes Which Affect Allelic Divergence Within Individuals

“…There is a fair number of studies reporting associations between particular MHC alleles and infectious diseases in humans [reviewed in (17)(18)(19) and other animals (reviewed in (8,10); e.g (14,(20)(21)(22)] consistent with NFDS/FS. However, associations between particular MHC alleles and infectious diseases in humans, and other animals (23), are sometimes inconsistent between studies and low sample sizes have been one explanation for such discrepancies. With more knowledge about the MHC region and the linkage of the genes therein it is now evident that chromosomal organization matters (19), hence analyses of effects of MHC on resistance/susceptibility to disease should preferably consider full MHC-haplotypes.…”

Associations between MHC class II variation and phenotypic traits in a free-living sheep population

“…Previous studies have demonstrated associations between MHC variation and antibody response in wild populations (summarized in (Gaigher, Burri et al 2019)). Some studies found significant associations (Bonneaud, Richard et al 2005, Charbonnel, Bryja et al 2010, Cutrera, Zenuto et al 2011, Gaigher, Burri et al 2019) while others did not (Ekblom, Hasselquist et al 2013, Cutrera, Zenuto et al 2014).…”

“…Previous studies have demonstrated associations between MHC variation and antibody response in wild populations (summarized in (Gaigher, Burri et al 2019)). Some studies found significant associations (Bonneaud, Richard et al 2005, Charbonnel, Bryja et al 2010, Cutrera, Zenuto et al 2011, Gaigher, Burri et al 2019) while others did not (Ekblom, Hasselquist et al 2013, Cutrera, Zenuto et al 2014). A recent study suggested that the disparity of findings in previous studies examining association between MHC variation and immunocompetence is likely caused by insufficient sample size and recommended a minimum sample size of 200 individuals to achieve sufficient power for testing associations of small effect size between MHC variation and immunocompetence (Gaigher, Burri et al 2019).…”

“…From this perspective, our sample size was large enough to have sufficient statistical power to test associations between MHC variation and immune measures (Table 2). In addition, previous studies investigating the association between MHC variation and antibody response have mainly used non-specific challenge, such as sheep red blood cell antigens (SRBC) and hemagglutinin, to elicit an antibody response (Bonneaud, Richard et al 2005, Cutrera, Zenuto et al 2011, Cutrera, Zenuto et al 2014, Gaigher, Burri et al 2019). An exception is a study of Great snipe ( Gallinago media ) that used diphtheria and tetanus toxoid as antigens (Ekblom, Hasselquist et al 2013).…”