Abstract
Genome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10−8/23) for statistical significance are identified. We investigate the implications of these GWAS findings in relation to biological mechanism, potential drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes are 16 known therapeutic-effect target genes for medications from 9 categories. Two of the medication classes studied are for disorders that have not previously been subject to large GWAS (hypothyroidism and gastro-oesophageal reflux disease).
Highlights
The percentage of participants taking medication increased with age and it was higher for female participants than for males, across all age groups
C09 medications have therapeutic effect on hypertension; of the 103 independent single nucleotide polymorphisms (SNPs) associated with C09 medications (P < 10−8/23), we identified SNPs previously linked to hypertension (7 SNPs)[7], systolic blood pressure (32 SNPs)[8], diastolic blood pressure (5 SNPs)[9] and pulse pressure (2 SNPs)[9]
Of the 55 independent SNPs associated with C10AA (HMG CoA reductase inhibitors)-associated SNPs (P < 10−8/23), 19 SNPs have been reported to be significantly associated with low-density lipoprotein cholesterol (LDLC)[10], supporting the known biological mechanism that statins are effective in lowering LDLC
Summary
Participants in the UK Biobank with a high genetic risk score (GRS) for different diseases/traits have a higher odds of taking corresponding medications than those with a low GRS (Fig. 3; Supplementary Table 4). GWAS associations for thyroid preparations (H03A), immunosuppressants (L04), adrenergics inhalants (R03A), glucocorticoids (R03BA) and antihistamines for systemic use (R06A) were enriched in immune cell types. Those of opioid analgesics (N02A) were enriched in central nervous system tissues, such as limbic system, those of antimigraine preparations (N02C) were enriched in cardiovascular tissue, and those of drugs affecting bone structure and mineralisation (M05B) were enriched in digestive cell type (Supplementary Data 3). N06A: Antidepressants N02C: Antimigraine preparations N02BA: Salicylic acid and derivatives N02BE: Anilides
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