"The variation of this SNP is shown in this new work to modify the scope of brain frontal lobe connectivity by altering the frequency of the functional establishment of either lateralized, long-range connections with the medial prefrontal cortex (predominant in "nonrisk" allele carriers) or more localized, bilateral connections (predominant in the "risk" allele carriers) during the performance of a reward-guided implicit learning task.
"The analytical approach is particularly powerful because it convincingly demonstrates these connectivity effects utilizing functional MRI in moderately sized sample sets. The marriage of genomics, neuroanatomy, and neuroimaging is still in its infancy, but already there are indications of the power of this approach both in this work and in work by others in the field.
"Dr. Scott-Van Zeeland and her colleagues suggest a biological mechanism for the development of autism and possibly other disorders in risk allele carriers. These findings present a possible way to further stratify carriers of the risk allele in future studies. For example, what might be different about individuals with autism who carry the risk allele but demonstrate prefrontal connectivity patterns that are more similar to nonrisk allele carriers? This question raises another issue. Based on the high minor allele frequency of rs2710102, carriers of the risk allele likely comprise more than half of the general population. How important is our individual genetics in determining the functional connectivity pattern, and what other genetic factors might predispose to such a pattern? Are these other genes autism risk candidates as well?
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"In spite of the questions that may remain to be answered, this work provides an important foothold for the mechanistic study of the extremely important public health problem of autism. One can hope that the future will hold additional studies involving neuroimaging and genetics in both healthy and diseased cohorts to help further dissect the functional basis for neuropsychiatric disease."
Dr. Huentelman’s laboratory focuses on autism, Alzheimer’s disease, aging, and diseases with a significant aging component. He has no relevant conflicts of interest.