A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Chromosome X-Wide Association Study Identifies Loci for Fasting Insulin and Height and Evidence for Incomplete Dosage Compensation
Tekijät: Tukiainen T, Pirinen M, Sarin AP, Ladenvall C, Kettunen J, Lehtimaki T, Lokki ML, Perola M, Sinisalo J, Vlachopoulou E, Eriksson JG, Groop L, Jula A, Jarvelin MR, Raitakari OT, Salomaa V, Ripatti S
Kustantaja: PUBLIC LIBRARY SCIENCE
Julkaisuvuosi: 2014
Journal: PLoS Genetics
Tietokannassa oleva lehden nimi: PLOS GENETICS
Lehden akronyymi: PLOS GENET
Artikkelin numero: ARTN e1004127
Vuosikerta: 10
Numero: 1
Sivujen määrä: 12
ISSN: 1553-7390
DOI: https://doi.org/10.1371/journal.pgen.1004127
Tiivistelmä
The X chromosome (chrX) analyses have often been neglected in large-scale genome-wide association studies. Given that chrX contains a considerable proportion of DNA, we wanted to examine how the variation in the chromosome contributes to commonly studied phenotypes. To this end, we studied the associations of over 400,000 chrX variants with twelve complex phenotypes, such as height, in almost 25,000 Northern European individuals. Demonstrating the value of assessing chrX associations, we found that as a whole the variation in the chromosome influences the levels of many of these phenotypes and further identified three new genomic regions where the variants associate with height or fasting insulin levels. In one of these three associated regions, the region near ITM2A, we observed that there is a sex difference in the genetic effects on height in a manner consistent with a lack of dosage compensation in this locus. Further supporting this observation, ITM2A has been shown to be among those chrX genes where the X chromosome inactivation is incomplete. Identifying phenotype associations in regions like this where chrX allele dosages are not balanced between men and women can be particularly valuable in helping us to understand why some characteristics differ between sexes.
The X chromosome (chrX) analyses have often been neglected in large-scale genome-wide association studies. Given that chrX contains a considerable proportion of DNA, we wanted to examine how the variation in the chromosome contributes to commonly studied phenotypes. To this end, we studied the associations of over 400,000 chrX variants with twelve complex phenotypes, such as height, in almost 25,000 Northern European individuals. Demonstrating the value of assessing chrX associations, we found that as a whole the variation in the chromosome influences the levels of many of these phenotypes and further identified three new genomic regions where the variants associate with height or fasting insulin levels. In one of these three associated regions, the region near ITM2A, we observed that there is a sex difference in the genetic effects on height in a manner consistent with a lack of dosage compensation in this locus. Further supporting this observation, ITM2A has been shown to be among those chrX genes where the X chromosome inactivation is incomplete. Identifying phenotype associations in regions like this where chrX allele dosages are not balanced between men and women can be particularly valuable in helping us to understand why some characteristics differ between sexes.
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