Genetic analysis of 25,000 Chinese mothers and infants reveals unique genes associated with disease risk

Genome-wide association studies have great potential for advancing our understanding of the genetic background of diseases, but so far, few association studies have focused on maternal and newborn diseases, and most have been based on predominantly European populations. To fill these gaps, researchers generated and analyzed full-genome DNA sequences from non-invasive prenatal blood tests collected from over 25,000 pregnant women, all of whom were Han Chinese.

The analyses revealed unique genetic variants associated with increased risk of maternal diseases including gestational diabetes, obesity, asthma, psoriasis, endometriosis, and hypothyroidism, the researchers report October 9 in the Cell Press journal Cell Genomics. Many (83%) of these genetic loci were associated with increased risk of multiple maternal diseases.

The team also identified 21 maternal genetic variants associated with increased risk of 35 different diseases in newborns. Two of these genes were associated with identical diseases in both mother and infant—dermatitis and acute sinusitis—while 33 others were associated with distinct disease symptoms in mother and child (for example, one variant associated with maternal hypothyroidism was associated with childhood gastroenteritis, colitis, and acute tonsillitis).

“Maternal and newborn health are intricately connected, and our study has provided important insights into the genetic basis of many maternal-neonatal comorbidities,” write the authors, who include Qiyuan Li and Yulin Zhou of Xiamen University. “These findings may facilitate the development of more targeted and personalized approaches to prenatal care and pediatric preventive strategies, ultimately improving maternal and neonatal health outcomes.”

The researchers began their analysis by sequencing the whole genomes of pregnant people from samples collected during non-invasive prenatal testing, a procedure that is used clinically to test for chromosomal abnormalities. Then, they paired these genetic data with the patients’ electronic health records to identify associations between genetic variants and different types of disease. Altogether, the researchers analyzed whole-genome sequences from 25,639 pregnant Chinese women and 14,151 newborns.  

The researchers say that their results highlight the potential for using non-invasive prenatal testing for large-scale genomic studies, which would be more cost-effective than currently used methods. The tests could also be used more broadly in the clinic, they say, but more research is needed to understand the mechanisms underlying the genetic associations revealed in the study.

“Currently, non-invasive prenatal testing is only used for detection of trisomy, while based on the results of this study, we can envision more extensive clinical usage of maternal circulating DNA in the prenatal diagnoses of genetic disorder and rare diseases,” the authors write.

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This research was supported by the National Natural Science Foundation of China, the National Key Research and Development Program of China, Fujian Province, and Fujian Provincial Health Commission.

Cell Genomics, Guo and Guo et al., “Phenome-wide association study in a Chinese population of 25,639 pregnant women reveals loci associated with maternal comorbidities and child health” https://www.cell.com/cell-genomics/fulltext/S2666-979X(24)00236-2  

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