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. 2023 May 27;13(1):181.
doi: 10.1038/s41398-023-02472-9.

Evolutionarily recent retrotransposons contribute to schizophrenia

Giorgia Modenini #  1 , Paolo Abondio #  1   2 , Guia Guffanti  3 , Alessio Boattini  4 , Fabio Macciardi  5
Affiliations

Evolutionarily recent retrotransposons contribute to schizophrenia

Giorgia Modenini et al. Transl Psychiatry. .

Abstract

Transposable elements (TEs) are mobile genetic elements that constitute half of the human genome. Recent studies suggest that polymorphic non-reference TEs (nrTEs) may contribute to cognitive diseases, such as schizophrenia, through a cis-regulatory effect. The aim of this work is to identify sets of nrTEs putatively linked to an increased risk of developing schizophrenia. To do so, we inspected the nrTE content of genomes from the dorsolateral prefrontal cortex of schizophrenic and control individuals and identified 38 nrTEs that possibly contribute to the emergence of this psychiatric disorder, two of them further confirmed with haplotype-based methods. We then performed in silico functional inferences and found that 9 of the 38 nrTEs act as expression/alternative splicing quantitative trait loci (eQTLs/sQTLs) in the brain, suggesting a possible role in shaping the human cognitive genome structure. To our knowledge, this is the first attempt at identifying polymorphic nrTEs that can contribute to the functionality of the brain. Finally, we suggest that a neurodevelopmental genetic mechanism, which involves evolutionarily young nrTEs, can be key to understanding the ethio-pathogenesis of this complex disorder.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Principal component analysis (PCA) of the DLPFC and 1KGP samples based only on non-reference TEs.
Pink: Europeans (CEU); green: Han Chinese in Beijing (CHB); brown: controls from the DLPFC (CTRL); red: Indian Telugus (ITU); yellow: Luhya in Kenya (LWK); blue: schizophrenic individuals from the DLPFC (SCZ); violet: Yoruba in Nigeria (YRI).
Fig. 2
Fig. 2. Admixture plot of the 20 DLPFC + 125 1KGP samples.
ADMIXTURE plot based only on nrTEs. K = 3 is shown (CV error = 0.37350).
Fig. 3
Fig. 3. Geographic distribution of the most significant (allele-wise) nrTEs.
Allele frequencies of Alus on chr4:17150918 (A), chr4:23511024 (B) and chr11:40727097 (C), compared to SVA on chromosome chr20:5268423 (D). Darker colors indicate the presence of the TE (+), while lighter colors indicate the absence (−). Following populations are displayed: Europeans (blue), Indian Telugus (red), Chinese (green) and Africans (yellow), represented by Luhya in Kenya and Yoruba in Nigeria. Allele frequencies for schizophrenic individuals and healthy controls are shown in violet and pink, respectively.
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