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

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Tyck till om SwePub Sök här!

Search: WFRF:(Reilly Muredach P) > (2014) > Farrall Martin > Wurtz Peter > Distribution and Me...

1 of 1
Previous record
Next record
To hitlist

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

Lim, Elaine T (author)

Würtz, Peter (author)

Havulinna, Aki S (author)

Palta, Priit (author)

Tukiainen, Taru (author)

Rehnström, Karola (author)

Esko, Tõnu (author)

Mägi, Reedik (author)

Inouye, Michael (author)

Lappalainen, Tuuli (author)

Chan, Yingleong (author)

Salem, Rany M (author)

Lek, Monkol (author)

Flannick, Jason (author)

Sim, Xueling (author)

Manning, Alisa (author)

Ladenvall, Claes (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Bumpstead, Suzannah (author)

Hämäläinen, Eija (author)

Aalto, Kristiina (author)

Maksimow, Mikael (author)

Salmi, Marko (author)

Blankenberg, Stefan (author)

Ardissino, Diego (author)

Shah, Svati (author)

Horne, Benjamin (author)

McPherson, Ruth (author)

Hovingh, Gerald K (author)

Reilly, Muredach P (author)

Watkins, Hugh (author)

Goel, Anuj (author)

Farrall, Martin (author)

Girelli, Domenico (author)

Reiner, Alex P (author)

Stitziel, Nathan O (author)

Kathiresan, Sekar (author)

Gabriel, Stacey (author)

Barrett, Jeffrey C (author)

Lehtimäki, Terho (author)

Laakso, Markku (author)

Groop, Leif (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Kaprio, Jaakko (author)

Perola, Markus (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

McCarthy, Mark I (author)

Boehnke, Michael (author)

Altshuler, David M (author)

Lindgren, Cecilia A (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Hirschhorn, Joel N (author)

Metspalu, Andres (author)

Freimer, Nelson B (author)

Zeller, Tanja (author)

Jalkanen, Sirpa (author)

Koskinen, Seppo (author)

Raitakari, Olli (author)

Durbin, Richard (author)

MacArthur, Daniel G (author)

Salomaa, Veikko (author)

Ripatti, Samuli (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Daly, Mark (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Palotie, Aarno (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

show less...

(creator_code:org_t)

2014-07-31
2014
English.
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7

Related links:: http://www.ncbi.nlm.... (free); show more...; http://dx.doi.org/10... (free); https://journals.plo...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

Find in a library

PLoS Genetics (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Lim, Elaine T; Würtz, Peter; Havulinna, Aki S; Palta, Priit; Tukiainen, Taru; Rehnström, Karol ...; show more...; Esko, Tõnu; Mägi, Reedik; Inouye, Michael; Lappalainen, Tuu ...; Chan, Yingleong; Salem, Rany M; Lek, Monkol; Flannick, Jason; Sim, Xueling; Manning, Alisa; Ladenvall, Claes; Bumpstead, Suzan ...; Hämäläinen, Eija; Aalto, Kristiina; Maksimow, Mikael; Salmi, Marko; Blankenberg, Ste ...; Ardissino, Diego; Shah, Svati; Horne, Benjamin; McPherson, Ruth; Hovingh, Gerald ...; Reilly, Muredach ...; Watkins, Hugh; Goel, Anuj; Farrall, Martin; Girelli, Domenic ...; Reiner, Alex P; Stitziel, Nathan ...; Kathiresan, Seka ...; Gabriel, Stacey; Barrett, Jeffrey ...; Lehtimäki, Terho; Laakso, Markku; Groop, Leif; Kaprio, Jaakko; Perola, Markus; McCarthy, Mark I; Boehnke, Michael; Altshuler, David ...; Lindgren, Cecili ...; Hirschhorn, Joel ...; Metspalu, Andres; Freimer, Nelson ...; Zeller, Tanja; Jalkanen, Sirpa; Koskinen, Seppo; Raitakari, Olli; Durbin, Richard; MacArthur, Danie ...; Salomaa, Veikko; Ripatti, Samuli; Daly, Mark; Palotie, Aarno; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: PLoS Genetics

By the university: Lund University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

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

Subject headings

Publication and Content Type

Find in a library

To the university's database

Find more in SwePub

Search outside SwePub