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

Farid Rajabli, Briseida E. Feliciano-Astacio, Holly N. Cukier, Liyong Wang, Anthony J. Griswold, Kara L. Hamilton-Nelson, Larry D. Adams, Vanessa C. Rodriguez, Pedro R. Mena, Sergio Tejada, Katrina Celis, Patrice L. Whitehead, Derek J. Van Booven, Natalia K. Hofmann, Parker L. Bussies, Michael Prough, Angel Chinea, Nereida I. Feliciano, Badri N. Vardarajan, Christiane ReitzJoseph H. Lee, Martin J. Prince, Ivonne Z. Jimenez, Richard P. Mayeux, Heriberto Acosta, Clifton L. Dalgard, Jonathan L. Haines, Jeffery M. Vance, Michael L. Cuccaro, Gary W. Beecham, Margaret A. Pericak-Vance

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)115.e1-115.e7
JournalNeurobiology of aging
Volume104
DOIs
StatePublished - Aug 2021

Keywords

  • Alzheimer disease
  • Chromosome 9
  • Genetic linkage
  • Puerto Ricans
  • Underserved populations

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

Fingerprint

Dive into the research topics of 'Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus'. Together they form a unique fingerprint.

Cite this