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

Overview of attention for article published in PLoS Genetics, July 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
6 news outlets
blogs
1 blog
twitter
91 X users
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2 patents
facebook
1 Facebook page

Citations

dimensions_citation
362 Dimensions

Readers on

mendeley
372 Mendeley
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8 CiteULike
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Title
Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
Published in
PLoS Genetics, July 2014
DOI 10.1371/journal.pgen.1004494
Pubmed ID
Authors

Elaine T. Lim, Peter Würtz, Aki S. Havulinna, Priit Palta, Taru Tukiainen, Karola Rehnström, Tõnu Esko, Reedik Mägi, Michael Inouye, Tuuli Lappalainen, Yingleong Chan, Rany M. Salem, Monkol Lek, Jason Flannick, Xueling Sim, Alisa Manning, Claes Ladenvall, Suzannah Bumpstead, Eija Hämäläinen, Kristiina Aalto, Mikael Maksimow, Marko Salmi, Stefan Blankenberg, Diego Ardissino, Svati Shah, Benjamin Horne, Ruth McPherson, Gerald K. Hovingh, Muredach P. Reilly, Hugh Watkins, Anuj Goel, Martin Farrall, Domenico Girelli, Alex P. Reiner, Nathan O. Stitziel, Sekar Kathiresan, Stacey Gabriel, Jeffrey C. Barrett, Terho Lehtimäki, Markku Laakso, Leif Groop, Jaakko Kaprio, Markus Perola, Mark I. McCarthy, Michael Boehnke, David M. Altshuler, Cecilia M. Lindgren, Joel N. Hirschhorn, Andres Metspalu, Nelson B. Freimer, Tanja Zeller, Sirpa Jalkanen, Seppo Koskinen, Olli Raitakari, Richard Durbin, Daniel G. MacArthur, Veikko Salomaa, Samuli Ripatti, Mark J. Daly, Aarno Palotie

Abstract

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 non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10⁻¹¹⁷). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.

X Demographics

X Demographics

The data shown below were collected from the profiles of 91 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 372 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 <1%
United Kingdom 2 <1%
Netherlands 1 <1%
Sweden 1 <1%
France 1 <1%
Italy 1 <1%
Finland 1 <1%
Unknown 363 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 90 24%
Student > Ph. D. Student 84 23%
Student > Master 34 9%
Student > Bachelor 27 7%
Professor > Associate Professor 19 5%
Other 59 16%
Unknown 59 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 116 31%
Biochemistry, Genetics and Molecular Biology 88 24%
Medicine and Dentistry 55 15%
Nursing and Health Professions 6 2%
Computer Science 6 2%
Other 34 9%
Unknown 67 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 107. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 September 2023.
All research outputs
#396,834
of 25,515,042 outputs
Outputs from PLoS Genetics
#233
of 8,975 outputs
Outputs of similar age
#3,391
of 239,544 outputs
Outputs of similar age from PLoS Genetics
#5
of 184 outputs
Altmetric has tracked 25,515,042 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,975 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.8. This one has done particularly well, scoring higher than 97% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 239,544 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.