@misc{10481/84926,
year = {2023},
month = {3},
url = {https://hdl.handle.net/10481/84926},
abstract = {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.},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Mental Health (NIMH)	R01MH109536


R01MH118278
R01MH124839


U01MH109536},
organization = {UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)},
organization = {Janette Mary O'Neil Research Fellowship},
organization = {National Health and Medical Research Council (NHMRC) of Australia},
organization = {Instituto de Salud Carlos III
Spanish Government},
organization = {European Regional Development Fund/European Social Fund A Way to Make Europe/Investing in Your Future},
organization = {Instituto de Salud Carlos III
Spanish Government},
organization = {European Regional Development Fund Funds from the European Commission, A Way of Making Europe},
organization = {Centro de Investigacion Biomedica en Red de Salud Mental, Madrid Regional Government},
organization = {Fundacion Familia Alonso	MR/L010305/1
MR/P005748/1},
organization = {Fundacion Alicia Koplowitz	1R01MH124851},
organization = {European Regional Development Fund Funds from the European Commission	R01MH100125
1I01CX000995},
organization = {Ministry of Health, Italy	P50MH066392},
organization = {Takeda Pharmaceutical Company Ltd},
organization = {Hoffmann-La Roche},
organization = {Hoffmann-La Roche},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA	1037196

1176716},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Mental Health (NIMH)	513861},
organization = {Australian Schizophrenia Research Bank	PI18/00238
PI18/00467
B2017/BMD-3740 AGES-CM-2
115916
777394},
organization = {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
R01MH106056},
publisher = {Springer Nature},
keywords = {Genetic association study},
keywords = {Genetics research},
keywords = {Schizophrenia},
title = {Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations},
doi = {10.1038/s41588-023-01305-1},
author = {Liu, Dongjing and Gutiérrez Martínez, Blanca and Molina Rivas, Esther and Cervilla Ballesteros, Jorge Antonio and Rivera Sánchez, Margarita},
}