Linkage disequilibrium means that alleles at different genetic loci are associated in population haplotypes. For two biallelic loci,The first quantity measures departure from independent allele frequencies; the second is the squared allelic correlation. Standardized linkage disequilibrium $D^{\prime }$ instead compares $D$ to its possible range at the given frequencies. High $|D^{\prime }|$ can coexist with low $r^2$, so it need not make one genetic marker a good predictor of another. Genetic linkage is a different notion: it describes within-family transmission and the recombination fraction.

The chromosome-21 study of Patil and colleagues, Science 2001 found consecutive single-nucleotide polymorphisms organized into regions with comparatively few common haplotypes; typically three haplotypes accounted for over 80% of the sampled chromosomes within a block. Such haplotype blocks can be represented efficiently by tag SNPs. Strong association within blocks and weaker association across boundaries give a useful description, though block boundaries depend on allele frequencies, population history, sampling and the operational definition of a block. They do not divide chromosomes into regions where genetic recombination is respectively impossible and certain.

The ancestry explanation uses an ancestral recombination graph. Going backwards, ancestral lineages coalesce, while a genetic recombination event splits one lineage's ancestral material into contributions from two parents. At a fixed genomic position, retaining only its ancestry gives a phylogenetic tree with the appropriate coalescent law. Nearby positions often retain much of the same tree; mutations on shared branches then produce correlated allele states. Breakpoints can change the local tree, weakening that shared history.

Under a simple random-mating two-locus model, linkage-disequilibrium decay under recombination gives $D_{t+1}=(1-r)D_t$. Actual populations also undergo genetic drift, population bottlenecks, mutation and migration, which can create or preserve association. Recombination rates themselves vary along chromosomes: McVean and colleagues, Science 2004 inferred strong local variation from sequence data. These observations motivate an ancestry model with spatially varying recombination, rather than treating physical distance as the only determinant of linkage disequilibrium.

For fine mapping, a typed genetic marker can show genetic association because it is correlated with a nearby causal genetic variant. Linkage-disequilibrium marker tagging makes a sparse first-stage scan possible, but several variants in one block can produce nearly indistinguishable association patterns. Historical recombination and diverse local genealogies can narrow the interval when denser genotyping is available.

An ancestral recombination graph turns that intuition into a likelihood calculation. One can place a proposed disease-origin event on a local ancestral branch and integrate over possible graphs, mutation histories and unobserved haplotypes. The local phylogenetic tree then relates disease-bearing chromosomes and predicts which markers should remain associated. In a Bayesian inference, uncertainty in ancestry, mutation location and demographic parameters enters the posterior distribution rather than being replaced by one guessed tree. Whole-graph inference is computationally demanding, and approximate or pairwise methods often supply practical estimates.

The useful distinction is between finding an associated region and identifying its causal variant. Strong linkage disequilibrium improves marker coverage but can limit resolution inside the associated region. Population stratification, ascertainment, rare variants and misspecified population history can also mislead an association analysis. Combining fine mapping with independent biological evidence is therefore stronger than interpreting an association peak as proof of causation.

For subject $i$, write ${\delta }_i=1_{\{T_i\le C_i\}}$, and define the counting process and pre-event at-risk process byUnder independent censoring and a common hazard, each observed event-free subject has conditional event probability $h(t)dt$ in a short interval. Therefore $\mathbb{E}(dN(t)\mid \text{past})=R(t)dH(t)$ to first order. Equivalently the compensator of a counting process is ${\int }_0^{t}R(s)dH(s)$. Dividing the observed increments by current exposure gives the estimating equation $d\hat{H}=dN/R$, henceHere $t_j$ are distinct event times, $d_j$ the number of events at that time, and $r_j=R(t_j)$ the number at risk immediately before it. One can also obtain the same increment by maximizing the local multiplicative-intensity likelihood $a^{d_j}{e}^{-r_{j}a}$: differentiation gives $a=d_j/r_j$. This derives the Nelson–Aalen estimator, rather than merely naming it.

A censored observation contributes to the denominator while under observation, and then leaves the risk set; it contributes no event jump. For tied events, use the single increment $d_j/r_j$, not $d_j$ successive one-event increments with shrinking denominators. If censoring and events share a recorded time, a convention is needed; counting the event before removing same-time censored subjects uses the pre-time risk set above. Rounded or interval-censored data may require a model suited to their observation mechanism.

For the distinct ordered observations in the question, let ${\delta }_j$ indicate whether $X_j$ is an event. The risk set at $X_j$ contains precisely the $n-j+1$ subjects whose recorded time is at least $X_j$. ThusTherefore the sum of the fitted integrated hazards at all observation times equals the observed number of events, the event-count identity for Nelson–Aalen cumulative hazards. The grouped Nelson–Aalen event-count identity extends the same argument to tied observations with their multiplicities and the stated risk-set convention.