A study in which IANEC has participated has carried out the largest homozygosity analysis performed for Alzheimer’s disease.

This study, in which IANEC has participated, represents the largest analysis of homozygosity conducted for Alzheimner´s disease (AD). Our estimates of homozygosity provide a robust evidence supporting that recessive allelic architecture might define a portion of AD heritability.

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.). We detected an increase of homozygosity in AD cases compared to controls.

We demonstrated the existence of an inbreeding effect in AD and efficiently captured a fraction of inbred individuals from outbred populations, providing an improved strategy to look for recessive alleles, and to conduct future large-scale homozygosity mapping studies in AD. Furthermore, the exploration of complementary sequencing data gave an added value to this research, providing a subset of potential candidates harboring recessive variants. In any case, the proposed candidates would need confirmation in larger series. Greater efforts and larger collections of individuals with GWAS and sequencing data are needed to confirm the presentfindings. Our understanding of the dynamics of population genomics in AD is far from complete, but long runs of homozygosity  analyses provide us with a means to go further and might be an alternative strategy to uncover the genetic loci underlying AD


Translational Psychiatry (2021) 11:142 https://doi.org/10.1038/s41398-020-01145-1