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Many linkage studies are performed in inbred populations, either small isolated populations or large populations with a long tradition of marriages between relatives. In such populations, there exist very complex genealogies with unknown loops. Therefore, the true inbreeding coefficient of an individual is often unknown. Good estimators of the inbreeding(More)
Alzheimer's disease is a genetically complex disorder, for which new putative susceptibility genes are constantly proposed in the literature. We selected 16 candidate genes involved in biological pathways closely related to the pathology, and for which a genetic association with Alzheimer's disease was previously detected: ACE, BACE1, BDNF, ECE1, HSPG2,(More)
The 1000 Genomes Project provides a unique source of whole genome sequencing data for studies of human population genetics and human diseases. The last release of this project includes more than 2,500 sequenced individuals from 26 populations. Although relationships among individuals have been investigated in some of the populations, inbreeding has never(More)
Substantial clinical variability is observed in many Mendelian diseases, so that patients with the same mutation may develop a very severe form of disease, a mild form or show no symptoms at all. Among the factors that may explain these differences in disease expression are modifier genes. In this paper, we review the different strategies that can be used(More)
The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched(More)
With the availability of very dense genome-wide maps of markers, multiple testing has become a major difficulty for genetic studies. In this context, the false-discovery rate (FDR) and related criteria are widely used. Here, we propose a finite mixture model to estimate the local FDR (lFDR), the FDR, and the false non-discovery rate (FNR) in(More)
Recent epidemiological, biological and genetic data indicate a relationship between cholesterol and Alzheimer's disease (AD) including the association of polymorphisms of ABCA1 (a gene that is known to participate in cholesterol and phospholipid transport) with AD prevalence. Based on these data, we postulated that genetic variation in the related and(More)
BACKGROUND The cladistic approach proposed by Templeton has been presented as promising for the study of the genetic factors involved in common diseases. This approach allows the joint study of multiple markers within a gene by considering haplotypes and grouping them in nested clades. The idea is to search for clades with an excess of cases as compared to(More)
Haplotype frequency estimation in population data is an important problem in genetics and different methods including expectation maximisation (EM) methods have been proposed. The statistical properties of EM methods have been extensively assessed for data sets with no missing values. When numerous markers and/or individuals are tested, however, it is(More)
Polymorphisms in the Nicastrin (NCSTN) gene have recently been associated with familial early-onset Alzheimer's disease (AD). The authors genotyped four NCTSN polymorphisms in a large cohort of 489 AD cases (including 158 sporadic early-onset AD cases and 95 familial early-onset AD cases) and 386 controls but failed to replicate the association between(More)