Genome-wide association study of 1,391 plasma metabolites in 6,136 Finnish men identifies 303 novel signals and provides biological insights into human diseases

Few studies have explored the impact of rare variants (minor allele frequency, MAF<1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1,391 plasma metabolites in 6,136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits.