Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
Metadatos
Mostrar el registro completo del ítemAutor
Liu, Dongjing; Gutiérrez Martínez, Blanca; Molina Rivas, Esther; Cervilla Ballesteros, Jorge Antonio; Rivera Sánchez, MargaritaEditorial
Springer Nature
Materia
Genetic association study Genetics research Schizophrenia
Fecha
2023-03-13Referencia bibliográfica
Liu, D., Meyer, D., Fennessy, B. et al. Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations. Nat Genet 55, 369–376 (2023). [https://doi.org/10.1038/s41588-023-01305-1]
Patrocinador
United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R01MH109536 R01MH118278 R01MH124839 U01MH109536; UK Research & Innovation (UKRI) Medical Research Council UK (MRC); Janette Mary O'Neil Research Fellowship; National Health and Medical Research Council (NHMRC) of Australia; Instituto de Salud Carlos III Spanish Government; European Regional Development Fund/European Social Fund A Way to Make Europe/Investing in Your Future; Instituto de Salud Carlos III Spanish Government; European Regional Development Fund Funds from the European Commission, A Way of Making Europe; Centro de Investigacion Biomedica en Red de Salud Mental, Madrid Regional Government; Fundacion Familia Alonso MR/L010305/1 MR/P005748/1; Fundacion Alicia Koplowitz 1R01MH124851; European Regional Development Fund Funds from the European Commission R01MH100125 1I01CX000995; Ministry of Health, Italy P50MH066392; Takeda Pharmaceutical Company Ltd; Hoffmann-La Roche; Hoffmann-La Roche; United States Department of Health & Human Services National Institutes of Health (NIH) - USA 1037196 1176716; United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) 513861; Australian Schizophrenia Research Bank PI18/00238 PI18/00467 B2017/BMD-3740 AGES-CM-2 115916 777394; Neuroscience Research Australia PI18/00213 CPII21/00008 MS16/00153 PI19/024 R01MH085542 R01MH093725 P50MH080405 R01MH097276 RO1MH-075916 P50M096891 P50MH084053S1 R37MH057881 AG02219 AG05138 MH06692 R01MH110921 R01MH109677 R01MH109897 U01MH103392 U01MH116442 ZIC MH002903 HHSN271201300031C R01AG067025 R01AG065582 R01AG050986 R01MH125246 R01MH106056Resumen
Schizophrenia (SCZ) is a chronic mental illness and among the most
debilitating conditions encountered in medical practice. A recent landmark
SCZ study of the protein-coding regions of the genome identified a
causal role for ten genes and a concentration of rare variant signals in
evolutionarily constrained genes1. This recent study—and most other
large-scale human genetics studies—was mainly composed of individuals
of European (EUR) ancestry, and the generalizability of the findings in
non-EUR populations remains unclear. To address this gap, we designed
a custom sequencing panel of 161 genes selected based on the current
knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases
and 10,555 controls of diverse ancestries. Replicating earlier work, we found
that cases carried a significantly higher burden of rare protein-truncating
variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48;
P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828
cases and 107,877 controls, this excess burden was largely consistent across
five ancestral populations. Two genes (SRRM2 and AKAP11) were newly
implicated as SCZ risk genes, and one gene (PCLO) was identified as shared
by individuals with SCZ and those with autism. Overall, our results lend
robust support to the rare allelic spectrum of the genetic architecture of SCZ
being conserved across diverse human populations.