Journal article

Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population

Elaine T Lim, Peter Wuertz, Aki S Havulinna, Priit Palta, Taru Tukiainen, Karola Rehnstrom, Tonu Esko, Reedik Magi, Michael Inouye, Tuuli Lappalainen, Yingleong Chan, Rany M Salem, Monkol Lek, Jason Flannick, Xueling Sim, Alisa Manning, Claes Ladenvall, Suzannah Bumpstead, Eija Hamalainen, Kristiina Aalto Show all

PLoS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2014


Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of no..

View full abstract

University of Melbourne Researchers


Awarded by European Commission

Awarded by Academy of Finland

Awarded by Australian National Health and Medical Research Council

Awarded by Wellcome Trust

Awarded by GoT2D

Awarded by GoT2D Wellcome Trust


Awarded by European Union

Awarded by Estonian Ministry of Science and Education

Awarded by US National Institute of Health

Awarded by University of Tartu

Awarded by European Regional Development Fund

Awarded by FP7 grant

Awarded by Lung GO Sequencing Project

Awarded by WHI Sequencing Project

Awarded by Broad GO Sequencing Project

Awarded by Seattle GO Sequencing Project

Awarded by Heart GO Sequencing Project

Awarded by NIH

Awarded by National Institute for Health Research



Funding Acknowledgements

We acknowledge support and funding from the following grants: the European Commission FP7 projects no. 201413 ENGAGE (to AP), project no. 242167 SynSys (to AP), Health-2010 -projects no. 261433 BioSHare (to AP) and project no. 261123 gEUVADIS (to AP), the Academy of Finland grants no. 251704 and 263401 (to AP), the Finnish Foundation for Cardiovascular Research (to AP), the Sigrid Juselius Foundation (to AP), NIH/RFA-HL-12-007 (to AP), the European Commission Health-2010-project no. 261433 BioSHare (to SR), the Academy of Finland grants no 255847 and no 251217 (to SR), the Finnish Foundation for Cardiovascular Research (to SR), the Sigrid Juselius Foundation (to SR), the Academy of Finland grant #139635 (to VS), the Finnish Foundation for Cardiovascular Research (to VS), the Australian National Health and Medical Research Council Early Career Fellowship no. 637400 (to MI), the Wellcome Trust Research Career Development Fellow 086596/Z/08/Z (to CML), GoT2D RC2-DK088389 (to DMA), GoT2D Wellcome Trust 090367 (to MIM), Wellcome Trust 098381 (to MIM), T2DGENES NIDDM U01-DK-085545 (to MIM), DK062370 (to MB), DK085584 (to MB), DK088389(to MB), Academy of Finland grants 141054, 265240, 263278 (to JK), Academy of Finland grant 250422 (to PW), the European Union's Seventh Framework Programme FP7/2007-2013 [HEALTH-F2-2011-278913, BiomarCaRE], the Targeted Financing from the Estonian Ministry of Science and Education SF0180142s08 (to AMe), the US National Institute of Health R01DK075787 (to JNH, AMe), the Development Fund of the University of Tartu grant SP1GVARENG (to AMe), the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN) grant 3.2.0304.11-0312 (to AMe), and FP7 grant 313010 (to AMe). We thank the GoT2D, T2D-GENES and MIGen ExA groups for providing replication data, as well as the GTEx Consortium and Geuvadis Consortium for the use of the RNA sequencing data, and NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). Exome Chip genotyping in the Myocardial infarction Genetics Exome Array Consortium (MIGen ExA) was supported by NIH RC2 HL-102925 (to SG and DMA) and an investigator-initiated research grant from Merck to SKa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.