Heritability of skewed X-inactivation in female twins is tissue-specific and associated with age

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作者：
Antonino Zito
Matthew N. Davies
Pei-Chien Tsai
Susanna Roberts
Rosa Andres-Ejarque
Stefano Nardone
Jordana T. Bell
Chloe C. Y. Wong
Kerrin S. Small
机构：
[1] King’s College London,Department of Twin Research & Genetic Epidemiology
[2] Ervaxx Limited,Department of Biomedical Sciences
[3] Chang Gung University,Genomic Medicine Research Core Laboratory
[4] Chang Gung Memorial Hospital,Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience
[5] King’s College London,St John’s Institute of Dermatology, Faculty of Life Science & Medicine
[6] King’s College London,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center
[7] Harvard Medical School,undefined
来源：
Nature Communications | / 10卷
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摘要：
Female somatic X-chromosome inactivation (XCI) balances the X-linked transcriptional dosages between the sexes. Skewed XCI toward one parental X has been observed in several complex human traits, but the extent to which genetics and environment influence skewed XCI is largely unexplored. To address this, we quantify XCI-skew in multiple tissues and immune cell types in a twin cohort. Within an individual, XCI-skew differs between blood, fat and skin tissue, but is shared across immune cell types. XCI skew increases with age in blood, but not other tissues, and is associated with smoking. XCI-skew is increased in twins with Rheumatoid Arthritis compared to unaffected identical co-twins. XCI-skew is heritable in blood of females >55 years old (h2 = 0.34), but not in younger individuals or other tissues. This results in a Gene x Age interaction that shifts the functional dosage of all X-linked heterozygous loci in a tissue-restricted manner.
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