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Long Runs of Homozygosity Linked to Alzheimer's Disease

Long Runs of Homozygosity Linked to Alzheimer's Disease

In Hispanic population, mean length of ROHs significantly greater, especially in familial AD

TUESDAY, Aug. 27 (HealthDay News) -- For Hispanic individuals, the mean length of runs of homozygosity (ROHs) is greater for those with Alzheimer's disease (AD), particularly familial AD, than for controls, according to research published online Aug. 26 in JAMA Neurology.

Mahdi Ghani, Ph.D., from the University of Toronto, and colleagues used genome-wide array data to identify ROHs of more than 1 megabase in a Caribbean Hispanic data set of 547 unrelated cases (48.8 percent with familial AD) and 542 controls. The data set included African-Hispanics (207 cases and 192 controls) and European-Hispanics (329 cases and 326 controls).

The researchers identified 17,137 autosomal regions with ROHs. Per person, the mean length of the ROH was significantly greater in cases versus controls, and the correlation was stronger for familial AD. Even after correction for multiple testing, among European-Hispanics, a consensus region at the EXOC4 locus correlated significantly with AD. The most significant but nominal association was observed for the well-known AD gene candidate CTNNA3 among the African-Hispanic subset.

"Our results show that ROHs could significantly contribute to the etiology of AD," the authors write. "Future studies would require the analysis of larger, relatively inbred data sets that might reveal novel recessive AD genes. The next step is to conduct sequencing of top significant loci in a subset of samples with overlapping ROHs."

Abstract (http://archneur.jamanetwork.com/article.aspx?articleid=1729659#Abstract )Full Text (subscription or payment may be required) (http://archneur.jamanetwork.com/article.aspx?articleid=1729659 )