rs11848381 (SAMD4A-AS1): Alzheimer's Imaging GWAS

Key takeaways

• rs11848381 sits near SAMD4A-AS1 (a long noncoding antisense RNA gene) and SAMD4A (Sterile Alpha Motif Domain Containing 4A)
• This variant was examined in an Alzheimer's disease GWAS using a combined amyloid-PET and hippocampal-volume score across 944 subjects
• The alternate allele reduces SAMD4A-AS1 expression in whole blood, based on GTEx data from 953 donors
• The study's primary genome-wide significant hit was a different variant, rs6850306 near LCORL; evidence directly tying rs11848381 to Alzheimer's disease traits is limited in the provided text
• No lifestyle factors have been directly linked to this variant in the available evidence

What the research says A genome-wide association study computed a multimodal neuroimaging disease progression score - built from cortical amyloid burden measured by PET and bilateral hippocampal volume from MRI - as a quantitative trait in n=944 subjects from the Alzheimer's Disease Neuroimaging Initiative, spanning Alzheimer's disease, mild cognitive impairment, and cognitively healthy diagnoses. The primary genome-wide significant finding was rs6850306 near LCORL (P=1.03 x 10^-8, beta for the disease progression score = -0.07 +/- 0.01), with its protective minor allele replicated against conversion from mild cognitive impairment to Alzheimer's disease in an independent cohort of n=911 (hazard ratio = 0.593, 95% CI = 0.387-0.907); rs11848381 at the SAMD4A-AS1 / SAMD4A locus was part of the variant landscape examined in this same imaging genetics framework. Population-level expression data from GTEx v11 show that the alternate allele at this locus reduces SAMD4A-AS1 expression specifically in whole blood (slope = -0.27, p=1.5 x 10^-11, n=953 donors) GTEx Portal.

Reported associations

• Alzheimer's disease multimodal imaging progression: rs11848381 was identified in the context of a GWAS that combined amyloid PET and hippocampal MRI into a single disease progression score across n=944 ADNI subjects; the study's primary genome-wide significant result was rs6850306 at LCORL, and specific association statistics for rs11848381 are not reported in the provided study text, so this link should be treated as preliminary.
• SAMD4A-AS1 expression in whole blood (eQTL): The alternate allele at rs11848381 is associated with reduced expression of SAMD4A-AS1 in whole blood tissue, with a slope of -0.27 across 953 GTEx donors (p=1.5 x 10^-11) GTEx Portal.

Evidence quality The source study employed a multimodal disease progression score in n=944 ADNI subjects and independently validated its primary locus in a separate cohort of n=911, indicating a methodologically rigorous GWAS framework; however, the specific evidence base for rs11848381 at the SAMD4A-AS1 / SAMD4A locus is not detailed in the provided study text, and no genome-wide significant p-value or effect size for this variant appears in the available abstract or introduction excerpts. The GTEx eQTL finding for SAMD4A-AS1 in whole blood (slope = -0.27, p=1.5 x 10^-11, n=953) is independently robust at FDR-significant confidence GTEx Portal, but eQTL data describe a gene-regulatory mechanism and do not by themselves establish phenotypic health consequences. Overall, evidence for rs11848381 should be considered preliminary until study-level association data for this specific variant are fully reported.

Tissue-specific expression effects

• SAMD4A-AS1: In whole blood, the alternate allele at rs11848381 is associated with reduced expression of this antisense RNA gene (slope = -0.27, p=1.5 x 10^-11, n=953 donors) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.