An utter refutation of the 'Fundamental Theorem of the HapMap'

摘要: The International HapMap Project was proposed in order to quantify linkage disequilibrium (LD) relationships among human DNA polymorphisms an assortment of populations, facilitate the process selecting a minimal set markers that could capture most signal from untyped genome-wide association study. central dogma can be summarized by argument if marker is tight LD with polymorphism directly impacts disease risk, as measured metric r2, then one would able detect between and sample size increased factor 1/r2 over needed effect functional variant directly. This ‘fundamental theorem’ holds, however, only assumes loci etiological are independent each other, they statistically all other factors (in exposure action), sampling prospective, estimates r2 accurate. None these standard operating assumptions, however. We describe ramifications implicit provide simple examples which effects unequivocally detected it were genotyped, even high never show disease, infinite sizes. Both theoretical empirical refutation studies thus presented.