Inbreeding among Caribbean Hispanics from the Dominican Republic and its effects on risk of Alzheimer disease

• Published in: Genetics in medicine Vol. 17; no. 8; pp. 639 - 643
• Main Authors: Vardarajan, Badri N., Schaid, Daniel J., Reitz, Christiane, Lantigua, Rafael, Medrano, Martin, Jiménez-Velázquez, Ivonne Z., Lee, Joseph H., Ghani, Mahdi, Rogaeva, Ekaterina, St George-Hyslop, Peter, Mayeux, Richard P.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2015; Elsevier Limited
• Subjects: 631/208/457; 692/699/375/132/1283; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Biomedicine; Case-Control Studies; Consanguinity; Dominican Republic - epidemiology; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Hispanic or Latino; Human Genetics; Humans; Laboratory Medicine; Male; Middle Aged; original-research-article; Polymorphism, Single Nucleotide; Risk Factors; Dominican Republic
• ISSN: 1098-3600; 1530-0366; 1530-0366
• DOI: 10.1038/gim.2014.161

Background: Inbreeding can be associated with a modification of disease risk due to excess homozygosity of recessive alleles affecting a wide range of phenotypes. We estimated the inbreeding coefficient in Caribbean Hispanics and examined its effects on risk of late-onset Alzheimer disease. Methods: The inbreeding coefficient was calculated in 3,392 subjects (1,451 late-onset Alzheimer disease patients and 1,941 age-matched healthy controls) of Caribbean Hispanic ancestry using 177,997 nearly independent single-nucleotide polymorphisms from genome-wide array. The inbreeding coefficient was estimated using the excess homozygosity method with and without adjusting for admixture. Results: The average inbreeding coefficient in Caribbean Hispanics without accounting for admixture was F = 0.018 (±0.048), suggesting a mating equivalent to that of second cousins or second cousins once removed. Adjusting for admixture from three parent populations, the average inbreeding coefficient was found to be 0.0034 (±0.019) or close to third-cousin mating. Inbreeding coefficient was a significant predictor of Alzheimer disease when age, sex, and APOE genotype were used as adjusting covariates ( P = 0.03). Conclusion: The average inbreeding coefficient of this population is significantly higher than that of the general Caucasian populations in North America. The high rate of inbreeding resulting in increased frequency of recessive variants is advantageous for the identification of rare variants associated with late-onset Alzheimer disease. Genet Med 17 8, 639–643.