RT Journal Article SR Electronic T1 The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem JF bioRxiv FD Cold Spring Harbor Laboratory SP 052381 DO 10.1101/052381 A1 Mehdi Maadooliat A1 Naveen K. Bansal A1 Jiblal Upadhya A1 Manzur R. Farazi A1 Zhan Ye A1 Xiang Li A1 Steven J. Schrodi YR 2016 UL http://biorxiv.org/content/early/2016/05/10/052381.abstract 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.