Table 1.
GWAS and instruments used to extract SNPs for inflammation (CRP, IL-6, IL-6R, sIL-6R, GlycA) and cognition (working memory, emotion recognition, response inhibition).
| Phenotype | GWAS/Instrument | N | SNP location | N SNP | 1SMR | 2SMR |
|---|---|---|---|---|---|---|
| Inflammation | ||||||
| Primary analysis | ||||||
| CRP | Ligthart et al. (2018) | 204,402 |
CRP gene cis SNPs |
6 | 6 | 6 |
| Han et al. (2020) | 418,642 |
CRP gene cis SNPs |
20 | 18 | 13 | |
| IL-6R | Ahluwalia et al. (2021) | 52,654 |
IL6R gene cis SNPs |
2 | 2 | 2 |
| sIL-6R | Rosa et al. (2019) | 3,301 | IL6R gene cis SNPs | 34 | 34 | 22 |
| GlycA | Borges et al. (2020) | 115,078 | Genome-wide SNPs |
87 | 82 | 82 |
| Secondary analysis | ||||||
| CRP | Ligthart et al. (2018) | 204,402 | Genome-wide SNPs |
78 | 76 | 77 |
| Han et al. (2020) | 418,642 | Genome-wide SNPs |
552 | 520 | 494 | |
| IL-6 |
Ahluwalia et al. (2021) | 52,654 | Genome-wide SNPs |
3 | 3 | 3 |
| IL-6R | Sarwar et al. (2012) | 27,185 | IL6R gene cis SNPs | 1 | 1 | 1 |
| Swerdlow et al. (2012) | ≤ 4,479/ SNP |
IL6R gene cis SNPs | 3 | 3 | 3 | |
| GlycA | Kettunen et al. (2016) | 19,270 | Genome-wide SNPs |
10 | 10 | 10 |
| Cognition | ||||||
| Working memory | Mahedy et al. (2021) | 2,471 | Genome-wide SNPs |
3 | 3 | N/A |
| Emotion recognition | Mahedy et al. (2021) | 2,560 | Genome-wide SNPs |
6 | 6 | N/A |
| Response inhibition | Mahedy et al. (2021) | 2,446 | Genome-wide SNPs |
6 | 6 | N/A |
| General cognitive ability | Lam et al. (2021) | 373,617 | Genome-wide SNPs | 250 | N/A | Range: 219–250 |
N, number of participants; SNP location (Genome-wide SNPs [independent significant genome-wide SNPs] or cisSNPs [SNPs within +/- 1mB from protein coding gene]), N, number of SNPs identified from each GWAS/instrument (see section 2.2.1.2 for criteria applied); 1SMR, Final N SNPs included in genetic risk scores (including proxies) for one-sample MR; 2SMR, Final N SNPs included in instruments (including proxies) for two-sample MR; CRP, c-reactive protein; IL-6, interleukin-6; IL-6R, interleukin-6 receptor, sIL-6R, soluble interleukin-6 receptor; GlycA, glycoprotein acetyls.Note:genetic variants for some instruments were pre-selected:Rosa et al. (2019)selected independent SNPs (r2 < 0.1) located within 250kb fromIL6R;Sarwar et al. (2012)selected one SNP (rs2228145) located withinIL6R;Swerdlow et al. (2012)selected independent SNPs located within 55kb fromIL6R. For CRP, we pre-specified theLigthart et al. (2018)GWAS in our pre-registration; however, as a larger GWAS was available (Han et al., 2020), we included this GWAS to increase statistical power. For location of protein coding gene, see Supplementary Table S14 footnote.