MR Dictionary

Synonyms: Ambiguous SNP

A sequence of DNA is a palindrome if the 5’ to 3’ (sense or forward) sequence is the same as the 3’ to 5’ (antisense or reverse). For example, the sequence ACCTAGGT (reading 5’ to 3’) is a palindrome because its complement (3’ to 5’) is TGGATCCA. A palindromic SNP (also known as an ‘ambiguous’ SNP) is a SNP in which the possible alleles for that SNP pair with each other in the double helix structure. When this occurs, alleles on the forward strand are the same as on the reverse strand (e.g., C/G on forward is G/C on the reverse, as shown in Figure 1.1).

In two-sample MR with summary (aggregate) data, it can be difficult to harmonize palindromic SNPs if it is unclear which way (5’ to 3’ or vice versa) the allele are presented in each genome-wide association studies (GWAS). For some palindromes, it is possible to infer which is the effect allele using the allele frequency information. Where this is not the case, the options are to (i) assume all SNPs in both GWASs have been presented in the 5’ to 3’ way based on knowledge of other SNPs that are non-palindromic or (ii) drop all palindromic SNPs for which it is not possible to infer the direction.

Schematic representation of chromosomes, DNA and genetic variants in a diploid cell. From Hartwig et al., with permission.
Figure 1.1 - Schematic representation of chromosomes, DNA and genetic variants in a diploid cell. From Hartwig et al., with permission.

References

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