SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age.
SHANK1 alone does not predict autism in infants, but multi-gene SHANK panels may still help genetic counselors.
01Research in Context
What this study did
The team looked at SHANK1 gene variants in Chinese Han infants. They wanted to see if these variants raise autism risk.
They also checked if SHANK1, SHANK2, and SHANK3 variants work together. This is called SNP-SNP interaction testing.
What they found
Single SHANK1 variants did not predict autism. The gene alone is not a red flag.
Yet combined variants across the three SHANK genes did show a weak signal. The genes may act as a team, not solo stars.
How this fits with other research
Wan et al. (2019) saw early social gaps in infants later diagnosed with ASD. Their review shows behavior, not genes, is the clearer early clue.
Sakurai et al. (2008) also found no link when they screened single SLC6A4 variants. Like SHANK1, one gene rarely tells the story.
Pugsley et al. (2024) tested non-coding autism SNPs in brain tissue and found no expression change. Together these papers warn: single-gene screens can miss the action.
Why it matters
Do not rely on one gene panel to rule autism in or out. Use broad genetic plus behavioral data. Watch social milestones at 6–12 months. If the family wants testing, suggest a full SHANK panel, not just SHANK1.
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02At a glance
03Original abstract
Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations.
Autism research : official journal of the International Society for Autism Research, 2019 · doi:10.1002/aur.2065