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Autism Spectrum Disorder Contributors Found in Affected East African Families

NEW YORK – Using whole-genome sequencing, a team led by University of Texas Southwestern Medical Center researchers has tracked down genetic contributors to autism spectrum disorder (ASD) in families from East Africa — a region believed to have elevated ASD rates based on prior studies of immigrant populations in other parts of the world.

"An important motivation for our study is the paucity of genomic studies that capture the genetic diversity on the African continent," senior and corresponding author Maria Chahrour, a genetics, neuroscience, and psychiatry researcher with the University of Texas Southwestern Medical Center, said in an email, adding that "as genetic findings move into the clinic this translates to healthcare disparities."

"We set out to investigate the genetic contribution to the increased ASD prevalence in children from East African origin," she explained, "and to contribute to the ongoing efforts to bridge the diversity gap."

As they reported in Cell Genomics on Thursday, the researchers did whole-genome sequencing on 129 individuals from 33 ASD-affected families of East African ancestry from Ethiopia, Eritrea, and Kenya, searching for ties between ASD risk and the more than 2.1 million private variants unearthed in the East African cohort.

"This is the first study to investigate the genetics of ASD in an African population," Chahrour said, noting that "ASD genetics studies have focused almost exclusively on populations of European ancestry."

In the process, the team tracked down rare, ASD-associated variants in genes such as CACNA1C, CHD7, FMR1, and TCF7L2 that were previously linked to ASD or other neurodevelopmental conditions, along with nearby variants believed to regulate such genes.

"We detected rare coding variants in 12 known ASD genes and [eight] genes associated with other neurodevelopmental disorders," Chahrour said. "We also detected 12 rare noncoding variants in the regulatory regions of ASD and neurodevelopmental disease genes."

Beyond that, the investigators tracked down rare variants in and around candidate ASD genes not reported in the past, though they cautioned that additional follow-up studies are needed to validate the newly proposed risk genes.

When the investigators used admixture mapping to dig into the ASD-related variants falling in sequences inherited from ancestral African or European populations in the participants, meanwhile, they tracked down a subset of 10 risk loci variants falling within African ancestry haplotypes.

"Our approach emphasizes the power of African genetic variation and admixture analysis to inform the architecture of complex disorders," the authors explained, noting that "increased ASD prevalence in this population suggests decreased heterogeneity in the underlying genetic etiology, enabling risk allele identification."

The investigators noted that larger studies will be needed in the future to not only identify structural variants and other alterations associated with ASD but also better characterize the prevalence of the neurodevelopmental conditions in different parts of Africa, since some current estimates are based on ASD rates in children of East African ancestry living in Europe or North America.

"[W]e grappled with the complete lack of ASD prevalence studies in the East African countries represented by our study participants (Ethiopia, Eritrea, and Kenya)," the authors wrote, adding that the "current work further emphasizes the need for ASD genetics and prevalence studies in Africa, and it contributes to the growing efforts aimed at understanding the genetics of ASD and other neurodevelopmental disorders in Africa."