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Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.

TitleLinkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.
Publication TypeJournal Article
Year of Publication2021
AuthorsRajabli F, Feliciano-Astacio BE, Cukier HN, Wang L, Griswold AJ, Hamilton-Nelson KL, Adams LD, Rodriguez VC, Mena PR, Tejada S, Celis K, Whitehead PL, Van Booven DJ, Hofmann NK, Bussies PL, Prough M, Chinea A, Feliciano NI, Vardarajan BN, Reitz C, Lee JH, Prince MJ, Jimenez IZ, Mayeux RP, Acosta H, Dalgard CL, Haines JL, Vance JM, Cuccaro ML, Beecham GW, Pericak-Vance MA
JournalNeurobiol Aging
Date Published2021 08
KeywordsAlzheimer Disease, C9orf72 Protein, Chromosomes, Human, Pair 9, Genetic Linkage, Genetic Variation, Genome-Wide Association Study, Hispanic or Latino, Humans, Nerve Tissue Proteins, Whole Genome Sequencing

The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.

Pubmed Link
Alternate JournalNeurobiol Aging
PubMed ID33902942
Grant ListR01 AG070864 / AG / NIA NIH HHS / United States
RF1 AG054074 / AG / NIA NIH HHS / United States

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