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


CONCLUSIONS
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.
1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA [2] The Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
Badri N
BN
Vardarajan
Mayo Clinic, Rochester, Minnesota, USA.
Daniel J
DJ
Schaid
1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA [2] The Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA [3] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA [4] Department of Neurology, Columbia University, New York, New York, USA.
Christiane
C
Reitz
1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA [2] Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Rafael
R
Lantigua
School of Medicine, Pontificia Universidad Catolica Madre y Maestra, Santiago, Dominican Republic.
Martin
M
Medrano
Geriatrics Program, Internal Medicine Department, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico.
Ivonne Z
IZ
Jiménez-Velázquez
1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA [2] The Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA [3] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
Joseph H
0000000220004821
JH
Lee
1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada [2] Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mahdi
M
Ghani
1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada [2] Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ekaterina
E
Rogaeva
1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada [2] Department of Medicine, University of Toronto, Toronto, Ontario, Canada [3] Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Peter
P
St George-Hyslop
1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA [2] The Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA [3] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA [4] Department of Neurology, Columbia University, New York, New York, USA [5] Department of Psychiatry, School of Public Health, Columbia University, New York, New York, USA.
Richard P
RP
Mayeux
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003241:Consanguinity; D004293:Dominican Republic / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors