Genevieve H L Roberts, Pamela R Fain, Stephanie A Santorico, Richard A Spritz
{"title":"Inverse relationship between polygenic risk burden and age of onset of autoimmune vitiligo.","authors":"Genevieve H L Roberts, Pamela R Fain, Stephanie A Santorico, Richard A Spritz","doi":"10.1016/j.ajhg.2024.09.007","DOIUrl":null,"url":null,"abstract":"<p><p>Vitiligo is a common autoimmune disease characterized by patches of depigmented skin and overlying hair due to destruction of melanocytes in the involved regions. We investigated the relationship between vitiligo risk and vitiligo age of onset (AOO) using a vitiligo polygenic risk score that incorporated the most significant SNPs from genome-wide association studies. We find that vitiligo genetic risk and AOO are strongly inversely correlated; subjects with higher common-variant polygenic risk tend to develop vitiligo at an earlier age. Nevertheless, the correlation is not simple. In individuals who carry a single high-risk major histocompatibility complex class II haplotype, the effect of additional polygenic risk on vitiligo AOO is reduced. Particularly among those with early-AOO vitiligo (onset ≤12 years of age), genetic risk can reflect contributions from high common-variant burden but also rare variants of high effect and sometimes both. While the heritability of vitiligo is relatively high, and we here show that genetic risk factors predict vitiligo AOO, vitiligo is never congenital, and thus environmental triggers also play an important role in disease onset.</p>","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of human genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.ajhg.2024.09.007","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Vitiligo is a common autoimmune disease characterized by patches of depigmented skin and overlying hair due to destruction of melanocytes in the involved regions. We investigated the relationship between vitiligo risk and vitiligo age of onset (AOO) using a vitiligo polygenic risk score that incorporated the most significant SNPs from genome-wide association studies. We find that vitiligo genetic risk and AOO are strongly inversely correlated; subjects with higher common-variant polygenic risk tend to develop vitiligo at an earlier age. Nevertheless, the correlation is not simple. In individuals who carry a single high-risk major histocompatibility complex class II haplotype, the effect of additional polygenic risk on vitiligo AOO is reduced. Particularly among those with early-AOO vitiligo (onset ≤12 years of age), genetic risk can reflect contributions from high common-variant burden but also rare variants of high effect and sometimes both. While the heritability of vitiligo is relatively high, and we here show that genetic risk factors predict vitiligo AOO, vitiligo is never congenital, and thus environmental triggers also play an important role in disease onset.
期刊介绍:
The American Journal of Human Genetics (AJHG) is a monthly journal published by Cell Press, chosen by The American Society of Human Genetics (ASHG) as its premier publication starting from January 2008. AJHG represents Cell Press's first society-owned journal, and both ASHG and Cell Press anticipate significant synergies between AJHG content and that of other Cell Press titles.