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Cruchaga & Goate reply

Nature volume 520, page E10 (2015)Cite this article

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replying to B. V. Hooli et al. Nature 520, 10.1038/nature14040 (2015)

In an accompanying Comment addressing our recent study1, Hooli et al.2 report a failure to replicate an association between the PLD3 Val232Met variant and Alzheimer's disease using a family-based design. They analysed 439 late-onset Alzheimer's disease families from the NIMH data set. Unfortunately, because the authors only report a P value and Z statistic it is difficult to interpret the result. The variant is present in 5 out of 439 families and shows a P = 0.02, but is apparently over-transmitted to unaffected individuals. However, it is unclear how old these unaffected individuals are relative to affected individuals in these pedigrees or whether the Met 232 allele was present in the affected parent. Although the variant segregated perfectly in our initial families, an odds ratio (OR) of two in sporadic cases indicates that this variant will not show perfect segregation with disease in most families, as is the case for APOE4. Furthermore, it has been reported that even known pathogenic variants do not always segregate with disease status in late-onset families due to the presence of pre-symptomatic individuals and phenocopies3,4,5,6.

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References

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Authors and Affiliations

  1. Department of Psychiatry, Washington University, St Louis, 63110, Missouri, USA

    Carlos Cruchaga & Alison M. Goate

  2. Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University St Louis, Missouri, 63110, USA

    Carlos Cruchaga & Alison M. Goate

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  1. Carlos Cruchaga
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  2. Alison M. Goate
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Correspondence to Carlos Cruchaga.

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Cruchaga, C., Goate, A. Cruchaga & Goate reply. Nature 520, E10 (2015). https://doi.org/10.1038/nature14041

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