rs10521233 (HS3ST3A1): Childhood Asthma Onset

Key takeaways

• A variant near the HS3ST3A1 (heparan sulfate glucosamine 3-O-sulfotransferase 3A1) and COX10-DT genes has been studied in relation to how early children develop asthma.
• Children carrying risk versions of the two lead variants in this chromosomal region had lower lung function and used more asthma medication over four years of follow-up.
• The research spanned four independent cohorts of children from North America, Costa Rica, and Sweden, totaling over 1,500 participants.
• The two strongest associated variants in the study reached genome-wide significance (p < 10^-8) across all four cohorts.
• Direct evidence for rs10521233 specifically is limited; its association with asthma onset is inferred from genetic proximity to the study's lead variants, not from a named finding in the available text.

What the research says A genome-wide association study (GWAS, a method that scans the entire genome to find genetic variants linked to a trait) examined the age of onset of childhood asthma in 573 non-Hispanic white children from the Childhood Asthma Management Program (CAMP), and replicated findings in three independent cohorts totaling 931 additional participants from Costa Rica (n=591), Sweden (n=107), and a second North American clinical trial (n=233). Two lead variants, rs9815663 (Fisher's p = 2.31 x 10^-8) and rs7927044 (p = 6.54 x 10^-9), were significantly associated with earlier asthma onset in the combined analysis, and rs9815663 remained significant in the replication cohorts alone; ten additional variants in linkage disequilibrium (a measure of how often genetic variants are inherited together due to physical proximity on the chromosome) with rs9815663 were also associated with earlier onset, with p-values ranging from 2.24 x 10^-7 to 8.22 x 10^-6. Children carrying at least one risk allele of the two lead variants showed lower lung function and higher asthma medication use across four years of follow-up in CAMP.

Reported associations

• Age of onset of childhood asthma: The HS3ST3A1 - COX10-DT genomic region was implicated in a four-cohort GWAS of childhood asthma onset; ten variants in genetic proximity to the lead signal rs9815663 were associated with earlier onset (p range: 2.24 x 10^-7 to 8.22 x 10^-6), though rs10521233 is not named individually in the available study text.
• Lung function: Children carrying at least one risk allele of the two lead variants (rs9815663 and rs7927044) in this region had lower lung function over a 4-year follow-up period in CAMP.
• Asthma medication use: Carrying at least one risk allele of the two lead variants was associated with higher asthma medication use during the same 4-year follow-up in CAMP.

Evidence quality The discovery cohort (CAMP, n=573) was limited to non-Hispanic white children, which restricts generalizability to other ancestries. Replication across three independent cohorts (n=931 combined) from ethnically and geographically diverse populations strengthens confidence in the broader chromosomal region. The two lead SNPs reached genome-wide significance (p < 5 x 10^-8) in combined analysis, and one (rs9815663) also remained significant in the replication cohorts alone. The ten secondary SNPs in genetic proximity to rs9815663 did not individually reach genome-wide significance (p range: 2.24 x 10^-7 to 8.22 x 10^-6). The available study text does not report specific association statistics for rs10521233, making the direct evidence for this particular variant preliminary and indirect. The lung function and medication findings apply specifically to carriers of risk alleles at the two lead SNPs, not to the broader set of secondary variants.

Lifestyle considerations No lifestyle considerations on file for this variant.