Cordioli, Mattia,

Daly, Mark,

FinnGen

Ganna, Andrea,

Havulinna, Aki S.,

Helkkula, Pyry,

Jukarainen, Sakari,

Karjalainen, Juha,

Kiiskinen, Tuomo,

Krebs, Kristi

Kurki, Mitja,

Lehisto, Arto,

Lund University.

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

Kiiskinen, Tuomo

Helkkula, Pyry

Karjalainen, Juha

Saarentaus, Elmo

Mars, Nina

Lehisto, Arto

Zhou, Wei

Cordioli, Mattia

Jukarainen, Sakari

Rämö, Joel T.

Mehtonen, Juha

Veerapen, Kumar

Räsänen, Markus

Ruotsalainen, Sanni

Maasha, Mutaamba

Niiranen, Teemu

Tuomi, Tiinamaija

Salomaa, Veikko

Kurki, Mitja

Pirinen, Matti

Palotie, Aarno

Daly, Mark

Ganna, Andrea

Havulinna, Aki S.

Ripatti, Samuli

Lund University Publications

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases

Swepub

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases [Elektronisk resurs]

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

Similar works

Full text

Available Versions

Lund University Publications

Swepub

Helsingin yliopiston digitaalinen arkisto