TY - JOUR
T1 - The significance of not finding a gene
AU - Province, M. A.
N1 - Funding Information:
This work was partially supported by National Institutes of Health grants GM28719 and HL54473.
PY - 2001
Y1 - 2001
N2 - As more investigators conduct extensive whole-genome linkage scans for complex traits, interest is growing in meta-analysis as a way of integrating the weak or conflicting evidence from multiple studies. However, there is a bias in the most commonly used meta-analysis linkage technique (i.e., Fisher's [1925] method of combining of P values) when it is applied to many nonparametric (i.e., model free) linkage results. The bias arises in those methods (e.g., variance components, affected sib pair, extremely discordant sib pairs, etc.) that truncate all "negative evidence against linkage" into the single value of LOD = 0. If incorrectly handled, this bias can artificially inflate or deflate the combined meta-analysis linkage results for any given locus. This is an especially troublesome problem in the context of a genome scan, since LOD = 0 is expected to occur over half the unlinked genome. The bias can be overcome (nearly) completely by simply interpreting LOD = 0 as a P value of 1/2ln(2) ≅ .72 in Fisher's formula.
AB - As more investigators conduct extensive whole-genome linkage scans for complex traits, interest is growing in meta-analysis as a way of integrating the weak or conflicting evidence from multiple studies. However, there is a bias in the most commonly used meta-analysis linkage technique (i.e., Fisher's [1925] method of combining of P values) when it is applied to many nonparametric (i.e., model free) linkage results. The bias arises in those methods (e.g., variance components, affected sib pair, extremely discordant sib pairs, etc.) that truncate all "negative evidence against linkage" into the single value of LOD = 0. If incorrectly handled, this bias can artificially inflate or deflate the combined meta-analysis linkage results for any given locus. This is an especially troublesome problem in the context of a genome scan, since LOD = 0 is expected to occur over half the unlinked genome. The bias can be overcome (nearly) completely by simply interpreting LOD = 0 as a P value of 1/2ln(2) ≅ .72 in Fisher's formula.
UR - http://www.scopus.com/inward/record.url?scp=0034887388&partnerID=8YFLogxK
U2 - 10.1086/323316
DO - 10.1086/323316
M3 - Article
C2 - 11481587
AN - SCOPUS:0034887388
SN - 0002-9297
VL - 69
SP - 660
EP - 663
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -