Wang Feiyi, Liu Aoxing, Yang Zhiyu, Vartiainen Pekka, Jukarainen Sakari, Koskela Satu, Oram Richard, Allen Lowri, Ritari Jarmo, Partanen Jukka, Perola Markus, Tuomi Tiinamaija, Ganna Andrea
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland; Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Cell Genom. 2025 Jun 11;5(6):100854. doi: 10.1016/j.xgen.2025.100854. Epub 2025 Apr 25.
Type 1 diabetes (T1D) and other autoimmune diseases (AIDs) often co-occur in families. Leveraging data from 58,284 family trios in Finnish nationwide registers (FinRegistry), we identified that, of 50 parental AIDs examined, 15 were associated with an increased T1D risk in offspring. These identified epidemiological associations were further assessed in 470,000 genotyped Finns from the FinnGen study through comprehensive genetic analyses, partitioned into human leukocyte antigen (HLA) and non-HLA variations. Using FinnGen's 12,563 trios, a within-family polygenic transmission analysis demonstrated that the aggregation of many parental AIDs with offspring T1D can be partially explained by HLA and non-HLA polymorphisms in a disease-dependent manner. We therefore proposed a parental polygenic score (PGS), incorporating both HLA and non-HLA polymorphisms, to characterize the cumulative risk pattern of T1D in offspring. This raises an intriguing possibility of using parental PGS, in conjunction with clinical diagnoses, to inform individuals about T1D risk in their offspring.
1型糖尿病（T1D）和其他自身免疫性疾病（AIDs）在家族中常常共同出现。利用芬兰全国登记数据库（芬兰登记处）中58284个家庭三联体的数据，我们发现，在所研究的50种亲代自身免疫性疾病中，有15种与子代患T1D的风险增加相关。通过全面的基因分析，在芬兰基因研究项目的47万名基因分型芬兰人中，对这些已确定的流行病学关联进行了进一步评估，基因分析分为人类白细胞抗原（HLA）变异和非HLA变异。利用芬兰基因研究项目的12563个三联体，一项家系内多基因传递分析表明，许多亲代自身免疫性疾病与子代T1D的聚集现象，可部分由疾病依赖型的HLA和非HLA多态性来解释。因此，我们提出了一种亲代多基因评分（PGS），它纳入了HLA和非HLA多态性，以描述子代T1D的累积风险模式。这就引发了一种有趣的可能性，即结合临床诊断，利用亲代PGS来告知个体其子女患T1D的风险。
