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Mendelian randomiza...
Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
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Porcu, E (author)
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Rueger, S (author)
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Lepik, K (author)
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show more...
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Agbessi, M (author)
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Ahsan, H (author)
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Alves, I (author)
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Andiappan, A (author)
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Arindrarto, W (author)
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Awadalla, P (author)
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Battle, A (author)
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Beutner, F (author)
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Bonder, MJ (author)
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Boomsma, D (author)
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Christiansen, M (author)
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Claringbould, A (author)
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Deelen, P (author)
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Esko, T (author)
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Fave, MJ (author)
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Franke, L (author)
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Frayling, T (author)
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Gharib, SA (author)
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Gibson, G (author)
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Heijmans, BT (author)
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Hemani, G (author)
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Jansen, R (author)
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Kahonen, M (author)
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Kalnapenkis, A (author)
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Kasela, S (author)
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Kettunen, J (author)
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Kim, Y (author)
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Kirsten, H (author)
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Kovacs, P (author)
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Krohn, K (author)
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Kronberg-Guzman, J (author)
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Kukushkina, V (author)
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Lee, B (author)
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Lehtimaki, T (author)
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Loeffler, M (author)
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Marigorta, UM (author)
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Mei, HL (author)
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Milani, L (author)
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Montgomery, GW (author)
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Muller-Nurasyid, M (author)
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Nauck, M (author)
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Nivard, M (author)
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Penninx, B (author)
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Perola, M (author)
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Pervjakova, N (author)
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Pierce, BL (author)
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Powell, J (author)
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Prokisch, H (author)
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Psaty, BM (author)
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Raitakari, OT (author)
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Ripatti, S (author)
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Rotzschke, O (author)
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Saha, A (author)
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Scholz, M (author)
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Schramm, K (author)
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Seppala, I (author)
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Slagboom, EP (author)
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Stehouwer, CDA (author)
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Stumvoll, M (author)
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- Sullivan, P (author)
- Karolinska Institutet
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't Hoen, PAC (author)
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Teumer, A (author)
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Thiery, J (author)
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Tong, L (author)
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Tonjes, A (author)
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van Dongen, J (author)
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van Iterson, M (author)
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van Meurs, J (author)
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Veldink, JH (author)
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Verlouw, J (author)
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Visscher, PM (author)
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Volker, U (author)
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Vosa, U (author)
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Westra, HJ (author)
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Wijmenga, C (author)
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Yaghootkar, H (author)
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Yang, J (author)
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Zeng, B (author)
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Zhang, FT (author)
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Beekman, M (author)
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Bot, J (author)
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Deelen, J (author)
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Hofman, BA (author)
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Hottenga, JJ (author)
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Isaacs, A (author)
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Jhamai, PM (author)
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Kielbasa, SM (author)
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Lakenberg, N (author)
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Luijk, R (author)
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Moed, M (author)
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Nooren, I (author)
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Pool, R (author)
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Schalkwijk, CG (author)
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Slagboom, PE (author)
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Suchiman, HED (author)
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Swertz, MA (author)
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Tigchelaar, EF (author)
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Uitterlinden, AG (author)
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van den Berg, LH (author)
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van der Breggen, R (author)
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van der Kallen, CJH (author)
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van Dijk, F (author)
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van Duijn, CM (author)
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van Galen, M (author)
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van Greevenbroek, MMJ (author)
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van Heemst, D (author)
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van Rooij, J (author)
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Van't Hof, P (author)
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van Zwet, EW (author)
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Vermaat, M (author)
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Verbiest, M (author)
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Verkerk, M (author)
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Zhernakova, DV (author)
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Zhernakova, S (author)
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Santoni, FA (author)
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Reymond, A (author)
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Kutalik, Z (author)
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(creator_code:org_t)
- 2019-07-24
- 2019
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3300-
- Related links:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
-
Porcu, E
-
Rueger, S
-
Lepik, K
-
Agbessi, M
-
Ahsan, H
-
Alves, I
-
show more...
-
Andiappan, A
-
Arindrarto, W
-
Awadalla, P
-
Battle, A
-
Beutner, F
-
Bonder, MJ
-
Boomsma, D
-
Christiansen, M
-
Claringbould, A
-
Deelen, P
-
Esko, T
-
Fave, MJ
-
Franke, L
-
Frayling, T
-
Gharib, SA
-
Gibson, G
-
Heijmans, BT
-
Hemani, G
-
Jansen, R
-
Kahonen, M
-
Kalnapenkis, A
-
Kasela, S
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Kettunen, J
-
Kim, Y
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Kirsten, H
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Kovacs, P
-
Krohn, K
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Kronberg-Guzman, ...
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Kukushkina, V
-
Lee, B
-
Lehtimaki, T
-
Loeffler, M
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Marigorta, UM
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Mei, HL
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Milani, L
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Montgomery, GW
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Muller-Nurasyid, ...
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Nauck, M
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Nivard, M
-
Penninx, B
-
Perola, M
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Pervjakova, N
-
Pierce, BL
-
Powell, J
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Prokisch, H
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Psaty, BM
-
Raitakari, OT
-
Ripatti, S
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Rotzschke, O
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Saha, A
-
Scholz, M
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Schramm, K
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Seppala, I
-
Slagboom, EP
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Stehouwer, CDA
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Stumvoll, M
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Sullivan, P
-
't Hoen, PAC
-
Teumer, A
-
Thiery, J
-
Tong, L
-
Tonjes, A
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van Dongen, J
-
van Iterson, M
-
van Meurs, J
-
Veldink, JH
-
Verlouw, J
-
Visscher, PM
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Volker, U
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Vosa, U
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Westra, HJ
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Wijmenga, C
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Yaghootkar, H
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Yang, J
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Zeng, B
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Zhang, FT
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Beekman, M
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Bot, J
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Deelen, J
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Hofman, BA
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Hottenga, JJ
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Isaacs, A
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Jhamai, PM
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Kielbasa, SM
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Lakenberg, N
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Luijk, R
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Moed, M
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Nooren, I
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Pool, R
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Schalkwijk, CG
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Slagboom, PE
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Suchiman, HED
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Swertz, MA
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Tigchelaar, EF
-
Uitterlinden, AG
-
van den Berg, LH
-
van der Breggen, ...
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van der Kallen, ...
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van Dijk, F
-
van Duijn, CM
-
van Galen, M
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van Greevenbroek ...
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van Heemst, D
-
van Rooij, J
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Van't Hof, P
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van Zwet, EW
-
Vermaat, M
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Verbiest, M
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Verkerk, M
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Zhernakova, DV
-
Zhernakova, S
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Santoni, FA
-
Reymond, A
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Kutalik, Z
-
show less...
- Articles in the publication
-
Nature communica ...
- By the university
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Karolinska Institutet