(IVW) estimate, will differ slightly from the TSLS estimate in finite samples, as the correlation between independent genetic variants will not exactly equal zero,23 but the two estimates will be equal asymptotically (that is, they both tend towards the same quantity as their sample sizes increase towards infinity). However, an advantage of the IVW estimate is that it can be calculated from summarized data, whereas the TSLS estimate requires individual-level data. We assume for the remainder of the manuscript that the genetic variants are uncorrelated in their distributions (that is, knowledge of one does not help to predict the value of any other), as typically in Mendelian randomization one variant is taken from each gene region. Distantly located variants are usually uncorrelated; correlations between variants that are physically close can be found using an online tool such as [http://www.broadinstitute.org/mpg/snap/ldsearchpw.php].
