Cordioli, Mattia

Daly, Mark

FinnGen

Ganna, Andrea

Havulinna, Aki S.

Helkkula, Pyry

Jukarainen, Sakari

Karjalainen, Juha

Kiiskinen, Tuomo

Krebs, Kristi

Kurki, Mitja

Lehisto, Arto

Maasha, Mutaamba

Mars, Nina

Mehtonen, Juha

Milani, Lili

Niiranen, Teemu

Palotie, Aarno

Pirinen, Matti

Ripatti, Samuli

Ruotsalainen, Sanni

Rämö, Joel T.

Räsänen, Markus

Saarentaus, Elmo

Salomaa, Veikko

Tuomi, Tiinamaija

Veerapen, Kumar

Zhou, Wei

English

Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P < 5 × 10–9) associated with medication use. Fine-mapping revealed 494 95% credible sets associated with the total number of medication purchases, changes in medication combinations or treatment discontinuation, including 46 credible sets in 40 loci not associated with the underlying treatment targets. The polygenic risk scores (PRS) for cardiometabolic risk factors were strongly associated with the medication-use behavior. A medication-use enhanced multitrait PRS for coronary artery disease matched the performance of a risk factor-based multitrait coronary artery disease PRS in an independent sample (UK Biobank, n = 343,676). In summary, we demonstrate medication-based strategies for identifying cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases

Lund University Publications

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases

Arvas, Mikko

Hyvärinen, Kati

Ritari, Jarmo

Partanen, Jukka

Helsingin yliopiston digitaalinen arkisto

https://helda.helsinki.fi/bitstream/handle/10138/355969/s41591_022_02122_5.pdf?sequence=1&isAllowed=y

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases

Abstract

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Lund University Publications

Helsingin yliopiston digitaalinen arkisto