SLPMeta-AnalysisMolecular autism2017

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.

PMID 28540026

WHAT IT FOUND

The main autism-only genetic analysis found no variant that met the study's very strict threshold.

Adding a replication sample produced a chromosome 10q24.32 signal, and separate schizophrenia comparisons showed shared genetic risk.

Key findings

01No marker exceeded the strict P <= 5 x 10^-8 threshold in the main worldwide meta-analysis.

02Combining the discovery autism data with the Danish iPSYCH sample identified a single marker that passed the strict threshold at rs1409313-T (OR = 1.12; 95% CI 1.08-1.16; P = 1.058 x 10^-8).

03The autism-schizophrenia cross-disorder meta-analysis identified 12 new loci that passed the strict threshold after loci already significant in schizophrenia were removed.

STILL TO COME

How it was doneWhat they foundWhat it means for SLPs

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What it does not show

The main autism-only analysis did not find any variant that passed the strict threshold, so the headline 10q24.32 signal depends on combining discovery data with a replication sample. Replication was weak: 11 of 180 markers were nominally significant in iPSYCH and 8 of 159 in deCODE/SEED, and neither nominal enrichment was significant. Some samples were not independent: the Simons Simplex Collection individuals were already in the discovery analysis, and the Swedish PAGES controls overlapped the schizophrenia GWAS, so PAGES was excluded from cross-disorder work. The genetic correlation with schizophrenia may be partly confounded by assortative mating, which the authors list as a possible artefact rather than proven shared biology. The study reports genetic associations and heritability estimates, not clinical outcomes. Many cohorts were trio-based, which the authors say can underestimate common-variant heritability and power for complex traits, especially with assortative mating. The analyses did not include sex as a covariate, and the case group had a male-to-female ratio of 4.9:1.

The easy way to misread this

Do not read the 10q24.32 finding as a clinical test for autism. It appeared only after combining discovery data with a replication sample, the main autism-only analysis was null, and the reported odds ratio was 1.12.

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