The effect of variation in the apolipoprotein B gene on plasma lipid and apolipoprotein B levels I. A likelihood‐based approach to cladistic analysis

Hallman, David; Visvikis, S.; Steinmetz, J.; Boerwinkle, Eric

doi:10.1111/j.1469-1809.1994.tb00724.x

Cited by 34 publications

(25 citation statements)

References 102 publications

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“…It may be that recombination in this DNA region (which is crucial for the correct physiology of apolipoprotein B) originates alleles unfavourable to longevity. On the other hand, in a study carried out on French families, it was found that recombination within the APOB gene appears to be relatively rare (Hallman et al 1994). Also analyses of the 3′APOB-VNTR polymorphism with EcoRI-RFLP (Table 5) and XbaI-RFLP (Table 6) showed that the linkage disequilibrium tends to be stronger in S than in C.…”

Section: Discussionmentioning

confidence: 95%

DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus

et al. 1997

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To identify possible genetic factors affecting human longevity we compared allele pools at two candidate loci for longevity between a sample of 143 centenarians (S) and a control sample of 158 individuals (C). The candidate loci were APOB and TPO, which code for apolipoprotein B and thyroid peroxidase, respectively. Both restriction fragment length (RFL) (XbaI 2488 and EcoRI 4154 ) and variable number of tandem repeat (VNTR) (3′APOB-VNTR) polymorphisms were analysed at the APOB locus; the TPO-VNTR polymorphism (intron 10) was analysed at the TPO locus. The main result of the investigation was that there is an association between the APOB locus and longevity that is revealed only when multiallelic polymorphisms are considered. In particular: (i) the frequency of 3′APOB-VNTR alleles with fewer than 35 repeats is significantly lower in cases than in controls; (ii) the linkage disequilibrium between the XbaI-RFLP and the EcoRI-RFLP is significantly different from 0 in cases but not in controls; (iii) the EcoRI-RFLP and XbaI-RFLP allele frequencies do not discriminate between cases and controls. The differences observed between case and control allele pools are specific to the APOB locus, since no significant difference was observed at the TPO locus.

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Section: Discussionmentioning

confidence: 95%

DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus

et al. 1997

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“…(5) Compute the significance level as the proportion of p (k) s that are less than p. -Reject the global H 0 of no significant edge effects if the significance is < ␣, for ␣ = 0.05 for example. Thi s example is from Hallman et al [19] and was adopted in Seltman et al [10]. The frequencies sum up to 1.001 and we normalize them in the computation.…”

Section: Resultsmentioning

confidence: 99%

“…Seltman et al [10] used an example of a locus consisting of five bi-allelic markers when introducing the original ET-TDT method. (This example was originally presented in Hallman et al [19] for a study of the relation between apolipoprotein B and cholesterol.) For ease of comparison, we continue to adopt the same example.…”

Section: The Bt Graph Representation For a Haplotype Locusmentioning

confidence: 99%

“…However, in such cases the edge effects will often be less sparse than under the true cladogram because a single causal mutation may now have to be represented by several non-zero Cladogram of haplotypes. This example is originally from Hallman et al [19] and was adopted in Seltman et al [10] .…”

Section: Sparse Edge Effects In Bt Graphs and L 1 Penalized Conditionmentioning

confidence: 99%

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A Sparse Transmission Disequilibrium Test for Haplotypes Based on Bradley-Terry Graphs

Wong²,

Owen³

2012

Hum Hered

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Background: Linkage and association analysis based on haplotype transmission disequilibrium can be more informative than single marker analysis. Several works have been proposed in recent years to extend the transmission disequilibrium test (TDT) to haplotypes. Among them, a powerful approach called the evolutionary tree TDT (ET-TDT) incorporates information about the evolutionary relationship among haplotypes using the cladogram of the locus. Methods: In this work we extend this approach by taking into consideration the sparsity of causal mutations in the evolutionary history. We first introduce the notion of a Bradley-Terry (BT) graph representation of a haplotype locus. The most important property of the BT graph is that sparsity of the edge set of the graph corresponds to small number of causal mutations in the evolution of the haplotypes. We then propose a method to test the null hypothesis of no linkage and association against sparse alternatives under which a small number of edges on the BT graph have non-nil effects. Results and Conclusion: We compare the performance of our approach to that of the ET-TDT through a power study, and show that incorporating sparsity of causal mutations can significantly improve the power of a haplotype-based TDT.

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“…Haplotype frequencies chosen for this sample of individuals (table 1) have been taken from a study [Hallman et al, 1994] determining the impact of apolipoprotein B (ApoB) polymorphism in cholesterol.…”

Section: Genotype Data Considered and Relationships Between Genotypesmentioning

confidence: 99%

Association in Multifactorial Traits: How to Deal with Rare Observations?

2004

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To detect the role of a candidate gene for a trait in a sample of individuals, we may test SNP haplotype or diplotype effects. For a limited sample size, many haplotype or diplotype categories may contain few individuals. This involves a power decrease when testing the association between the trait and the haplotypes or diplotypes as these categories provide little additional information while increasing the degrees of freedom. The present paper proposes a new strategy to group rare categories based on a measure of similarity between haplotypes or diplotypes and compares it to two other possible strategies to deal with rare categories: a SNP selection strategy based on haplotype diversity, and a grouping strategy that pools all rare categories into a single baseline group. This comparison is performed by means of simulation under four scenarios. We show that this new strategy shows the largest increase in power irrespective of the model underlying the candidate gene in the studied trait. This strategy therefore provides a powerful alternative to currently used methods to reduce the number of rare categories.

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The effect of variation in the apolipoprotein B gene on plasma lipid and apolipoprotein B levels I. A likelihood‐based approach to cladistic analysis

Cited by 34 publications

References 102 publications

DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus

DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus

A Sparse Transmission Disequilibrium Test for Haplotypes Based on Bradley-Terry Graphs

Association in Multifactorial Traits: How to Deal with Rare Observations?

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