PT - JOURNAL ARTICLE AU - Mehdi Maadooliat AU - Naveen K. Bansal AU - Jiblal Upadhya AU - Manzur R. Farazi AU - Zhan Ye AU - Xiang Li AU - Steven J. Schrodi TI - The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem AID - 10.1101/052381 DP - 2016 Jan 01 TA - bioRxiv PG - 052381 4099 - http://biorxiv.org/content/early/2016/05/10/052381.short 4100 - http://biorxiv.org/content/early/2016/05/10/052381.full AB - Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases. Here, we present a simple relationship between disease association statistics and the decline of linkage disequilibrium from a causal site. A complete derivation of this relationship from a general disease model is shown for very large sample sizes. Quite interestingly, this relationship holds across all modes of inheritance. Extensive Monte Carlo simulations using a disease genetics model applied to chromosomes subjected to a standard model of recombination are employed to better understand the variation around this fine mapping theorem due to sampling effects. We also use this relationship to provide a framework for estimating properties of a non-interrogated causal site using data at closely linked markers. We anticipate that understanding the patterns of disease association decay with declining linkage disequilibrium from a causal site will enable more powerful fine mapping methods.