biostudies-literatureRajabli FNIA NIH HHSBrightFocus FoundationNational Institutes of Health115.e1-115.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC8851406biostudies-literatureUnknown104The 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 withNeurobiology of agingLinkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.PMC8851406P30 AG066462R01 AG070864U01 AG057659RF1 AG054074U01 AG058654Celis KBussies PLMena PRChinea ARodriguez VCReitz CGriswold AJHaines JLWang LCuccaro MLPericak-Vance MARajabli FAcosta HVan Booven DJHofmann NKCukier HNPrince MJFeliciano NIVardarajan BNLee JHMayeux RPAdams LDDalgard CLVance JMTejada SBeecham GWHamilton-Nelson KLWhitehead PLPrough MJimenez IZFeliciano-Astacio BEfalseLinkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.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 with2021-01-01T00:00:00Z2021 Aug2026-05-08T11:36:39.823Z2025-04-06T09:24:12.978ZS-EPMC88514063390294210.1016/j.neurobiolaging.2021.02.019