A saturated map of common genetic variants associated with human height
23andMe Research Team; VA Million Veteran Program; DiscovEHR (DiscovEHR and MyCode Community Health Initiative); eMERGE (Electronic Medical Records and Genomics Network); Lifelines cohort study; The PRACTICAL Consortium; Understanding Society Scientific Group; Yengo, Loïc; Vedantam, Sailaja; Marouli, Eirini; Sidorenko, Julia; Bartell, Eric; Sakaue, Saori; Graff, Marielisa; Eliasen, Anders U.; Jiang, Yunxuan; Raghavan, Sridharan; Miao, Jenkai; Arias, Joshua D.; Graham, Sarah E.; Mukamel, Ronen E.; Spracklen, Cassandra N.; Yin, Xianyong; Chen, Shyh Huei; Ferreira, Teresa; Highland, Heather H.; Ji, Yingjie; Karaderi, Tugce; Lin, Kuang; Lüll, Kreete; Malden, Deborah E.; Medina-Gomez, Carolina; Machado, Moara; Moore, Amy; Rüeger, Sina; Sim, Xueling; Vrieze, Scott; Ahluwalia, Tarunveer S.; Akiyama, Masato; Allison, Matthew A.; Alvarez, Marcus; Andersen, Mette K.; Ani, Alireza; Appadurai, Vivek; Arbeeva, Liubov; Bhaskar, Seema; Bielak, Lawrence F.; Bollepalli, Sailalitha; Bonnycastle, Lori L.; Bork-Jensen, Jette; Bradfield, Jonathan P.; Hansen, Thomas F.; Lyytikäinen, Leo Pekka; Mishra, Pashupati P.; Kähönen, Mika; Lehtimäki, Terho; Tuomilehto, Jaakko (2022)
23andMe Research Team
VA Million Veteran Program
DiscovEHR (DiscovEHR and MyCode Community Health Initiative)
eMERGE (Electronic Medical Records and Genomics Network)
Lifelines cohort study
The PRACTICAL Consortium
Understanding Society Scientific Group
Yengo, Loïc
Vedantam, Sailaja
Marouli, Eirini
Sidorenko, Julia
Bartell, Eric
Sakaue, Saori
Graff, Marielisa
Eliasen, Anders U.
Jiang, Yunxuan
Raghavan, Sridharan
Miao, Jenkai
Arias, Joshua D.
Graham, Sarah E.
Mukamel, Ronen E.
Spracklen, Cassandra N.
Yin, Xianyong
Chen, Shyh Huei
Ferreira, Teresa
Highland, Heather H.
Ji, Yingjie
Karaderi, Tugce
Lin, Kuang
Lüll, Kreete
Malden, Deborah E.
Medina-Gomez, Carolina
Machado, Moara
Moore, Amy
Rüeger, Sina
Sim, Xueling
Vrieze, Scott
Ahluwalia, Tarunveer S.
Akiyama, Masato
Allison, Matthew A.
Alvarez, Marcus
Andersen, Mette K.
Ani, Alireza
Appadurai, Vivek
Arbeeva, Liubov
Bhaskar, Seema
Bielak, Lawrence F.
Bollepalli, Sailalitha
Bonnycastle, Lori L.
Bork-Jensen, Jette
Bradfield, Jonathan P.
Hansen, Thomas F.
Lyytikäinen, Leo Pekka
Mishra, Pashupati P.
Kähönen, Mika
Lehtimäki, Terho
Tuomilehto, Jaakko
2022
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202211028111
https://urn.fi/URN:NBN:fi:tuni-202211028111
Kuvaus
Peer reviewed
Tiivistelmä
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Kokoelmat
- TUNICRIS-julkaisut [16983]