1 research outputs found
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
Background Over the past decade genome-wide association studies (GWAS) have
been applied to aid in the understanding of the biology of traits. The success
of this approach is governed by the underlying effect sizes carried by the
true risk variants and the corresponding statistical power to observe such
effects given the study design and sample size under investigation. Previous
ASD GWAS have identified genome-wide significant (GWS) risk loci; however,
these studies were of only of low statistical power to identify GWS loci at
the lower effect sizes (odds ratio (OR) <1.15). Methods We conducted a large-
scale coordinated international collaboration to combine independent
genotyping data to improve the statistical power and aid in robust discovery
of GWS loci. This study uses genome-wide genotyping data from a discovery
sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary
statistics from two replication sets (7783 ASD cases and 11359 controls; and
1369 ASD cases and 137308 controls). Results We observe a GWS locus at
10q24.32 that overlaps several genes including PITX3, which encodes a
transcription factor identified as playing a role in neuronal differentiation
and CUEDC2 previously reported to be associated with social skills in an
independent population cohort. We also observe overlap with regions previously
implicated in schizophrenia which was further supported by a strong genetic
correlation between these disorders (Rg = 0.23; P = 9 × 10−6). We further
combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the
recent PGC schizophrenia GWAS to identify additional regions which may be
important in a common neurodevelopmental phenotype and identified 12 novel GWS
loci. These include loci previously implicated in ASD such as FOXP1 at 3p13,
ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23.
Conclusions This study is an important step in the ongoing endeavour to
identify the loci which underpin the common variant signal in ASD. In addition
to novel GWS loci, we have identified a significant genetic correlation with
schizophrenia and association of ASD with several neurodevelopmental-related
genes such as EXT1, ASTN2, MACROD2, and HDAC4