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#LOD score

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Linkage and Mapping

Linkage is considered significant when LOD score is

Human genetics requires stringent criterion because 23 chromosome pairs create many opportunities for chance cosegregation. Statistical tradition established LOD 3 as significant and LOD -2 as exclusion after Newton Morton analysis of prior odds. At LOD 3 likelihood favoring linkage exceeds 1000:1, compensating prior odds of unlinked loci about 1:50 and providing genome-wide Type I error control near 0.05. Below 3 evidence considered suggestive but inconclusive, prompting collection additional families. For complex traits newer threshold 3.3 from Lander and Kruglyak accounts higher multiple testing burden in genome scans.

Ref: Lander & Kruglyak, Nature Genetics 1995 Thresholds; Lewis, Human Genetics, Chapter 6 LOD Significance

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Linkage and Mapping

LOD score of 3 indicates linkage is

LOD transformation uses base 10 logarithm, so LOD = log10[Odds]. Inverting logarithm gives Odds = 10^LOD. Therefore LOD 3 corresponds to 10^3 = 1000, meaning data observation is one thousand times more probable if loci are linked at estimated recombination fraction than if unlinked. This odds interpretation motivated choice threshold because random human genome loci have prior 50:1 probability unlinked, thus 1000:1 yields genome-wide significance approx p 0.05 after accounting multiplicity. LOD -2 similarly corresponds to 100:1 odds against linkage, serving exclusion criterion.

Ref: Hartl & Jones, Genetics: Principles and Analysis, 6th ed., Chapter: LOD Score Interpretation 1000:1

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Linkage and Mapping

LOD score is used to assess

LOD score, logarithm of odds, provides statistical evaluation of likelihood that two loci are linked at certain recombination fraction theta versus unlinked theta 0.5. In human pedigrees experimental crosses impossible, so likelihoods computed from family segregation data combining phase information, marker informativeness and penetrance models. Log10 ratio summed across families yields cumulative evidence for linkage across kindreds. Positive values favor linkage, negative values exclude linkage. Concept introduced by Morton and applied widely for mapping Mendelian disease genes before dense molecular maps, remaining fundamental for parametric linkage analysis.

Ref: Morton, LOD Score Method, Griffiths et al., Introduction to Genetic Analysis, 12th ed., Chapter 4: LOD for Human Linkage

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