Analysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP.

TitleAnalysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP.
Publication TypeJournal Article
Year of Publication2018
AuthorsNafikov RA, Nato AQ, Sohi H, Wang B, Brown L, Horimoto AR, Vardarajan BN, Barral SM, Tosto G, Mayeux RP, Thornton TA, Blue E, Wijsman EM
JournalGenet Epidemiol
Volume42
Issue6
Pagination500-515
Date Published2018 09
ISSN1098-2272
KeywordsAlzheimer Disease, Caribbean Region, Ethnic Groups, Family, Female, Gene Frequency, Gene Pool, Genetic Linkage, Genetics, Population, Hispanic Americans, Humans, Lod Score, Male, Models, Genetic, Pedigree, Phylogeny, Principal Component Analysis, Sequence Analysis, DNA
Abstract

Multipoint linkage analysis is an important approach for localizing disease-associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use marker allele frequencies determined by admixture proportions averaged over the entire sample. However, admixture proportions vary among pedigrees and throughout the genome in a family-specific manner. Here, we evaluate several approaches to model admixture in linkage analysis, providing different levels of detail about ancestral origin. To perform our evaluations, for specification of marker allele frequencies, we used data on 67 Caribbean Hispanic admixed families from the Alzheimer's Disease Sequencing Project. Our results show that choice of admixture model has an effect on the linkage analysis results. Variant-specific admixture proportions, computed for individual families, provide the most detailed regional admixture estimates, and, as such, are the most appropriate allele frequencies for linkage analysis. This likely decreases the number of false-positive results, and is straightforward to implement.

DOI10.1002/gepi.22133
Alternate JournalGenet. Epidemiol.
PubMed ID29862559
PubMed Central IDPMC6160322
Grant List5U01AG049507-04 / NH / NIH HHS / United States
U01 AG049507 / AG / NIA NIH HHS / United States
/ AG / NIA NIH HHS / United States
5U01AG049505-04 / NH / NIH HHS / United States
5U01AG049506-04 / NH / NIH HHS / United States
5P50AG005136-34 / NH / NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
/ / U.S. Department of Health and Human Services / International
R01 AG033193 / AG / NIA NIH HHS / United States
RF1 AG015473 / AG / NIA NIH HHS / United States
U01 AG049506 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States