Throughout the past decade, a great number of studies have been published searching for a gene-disease association. Ioannidis et al, studying a variety of diseases, pointed out that the first time such a relation is shown it correlates moderately with later results.¹

Sporadic Alzheimer’s disease (AD) has been extensively studied searching for gene causation.² Apart from the well established relation with ApoE ε-4 genotype, other gene candidates have weaker associations with AD and their role remains controversial. In fact, results from case-control studies are frequently contradictory and meta-analyses have been conducted to clarify whether a gene-AD association exists.³

The goal of this paper is to describe how the odds ratio between a gene and AD changes as new studies are published.

METHOD

We included case-control studies published before July 2003 on AD and the following polymorphisms: myeloperoxidase 7 (6 studies),^4–8 low density lipoprotein receptor related protein gene (LRP) exon 3 polymorphism (10 studies),^9–18 Glu298Asp polymorphism in the endothelial nitric oxide synthetase (NOS-3) (10 studies),^8,16,19–26 and cathepsin D (14 studies).^8,16,27–37 A …