Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach

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© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Table I. Reference intervals for platelet activity assays in pregnant women taking low-dose aspirin. (Separate intervals were derived for Randox for pregnant women at high risk of preeclampsia versus those at low risk, from the Liverpool and Dublin cohorts, respectively).

Method	2.5^th Quantile value (Lower 90% CI- Upper 90% CI)	50^th Quantile value (Lower 90% CI- Upper 90% CI)	97.5^th Quantile value (Lower 90% CI-Upper 90% CI)
Randox (high-risk) N = 126	187 (119–259)	1193 (1040–1452)	7152 (5773–12656)
Randox (low-risk) N = 157	830 (0–876)	1343 (1115–2561)	4264 (3719-Inf)
Platelet Solutions N = 126	96 (Inf-109)	144 (122–258)	632 (583-Inf)
Multiplate ASPI N = 157	27 (16–37)	54 (26–80)	150 (140–157)
Multiplate ADP N = 157	29 (24–31)	68 (63–73)	114 (110–126)
Multiplate ADP3.3 N = 157	22 (12–24)	48 (45–50)	93 (90–125)
PFA-100 N = 157	80 (75–82)	111 (103–116)	180 (166–227)

Figure 1. Distribution of individual patient results for urinary 11-dehydrothromboxane B2 (11DTXB2) (Randox laboratories). The three groups contain all three gestational ages included in the study.

Figure 2. GWAS meta-analysis findings of Liverpool and Dublin pregnancy cohorts using METAL software (Willer et al., 2010). a) Manhattan plot urinary 11-dehydrothromboxane B2 measures of aspirin compliant patients (n = 182). The top red threshold indicates genome-wide significance threshold of p < 5 x 10-8, the lower blue threshold indicates suggestive threshold p < 1 x 10-5. R package, qqman, was utilized to produce this Manhattan plot (Turner, 2018). Regional plots generated using LocusZoom (Pruim et al., 2010): b) chromosome 3 (rs62246396, SETD2); c) chromosome 1 (rs1749777, DAB1) indicating multiple SNPs in linkage disequilibrium; d) chromosome 14 (rs7143033, SLC25A21); and e) chromosome 7 (rs10156113, CACNA2D1) with several SNPs in linkage disequilibrium.