PDF(Pubmed)
Abstract：
BACKGROUND: Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism.
METHODS: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios.
RESULTS: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10-7), rs45580033 (ASB2, p = 4.2 × 10-10), and rs75426652 (LHPP, p = 7.2 × 10-14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants.
CONCLUSIONS: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.
METHODS: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios.
RESULTS: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10-7), rs45580033 (ASB2, p = 4.2 × 10-10), and rs75426652 (LHPP, p = 7.2 × 10-14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants.
CONCLUSIONS: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.
摘要：
背景：关于神经管缺陷遗传风险因素的人类研究，与存活儿童的长期健康后果相关的严重出生缺陷，在包括叶酸代谢在内的特定生物学途径中，主要限于候选基因的子集。
方法：在本研究中，我们调查了跨越基因组的遗传变异与脊柱裂风险的关联(即，2016年12月至2022年12月在孟加拉国进行的一项病例对照研究中，招募了一部分家庭的脊髓膜膨出和脑膜膨出），在遗传研究中通常代表性不足的人群。使用Illumina全局筛选阵列分析唾液DNA样品。我们进行了遗传关联分析，以比较112例和121例对照儿童的等位基因频率。272位母亲128个三重奏
结果：在仅使用三重奏的传输不平衡测试分析中，我们确定了三个新的外显子脊柱裂风险位点，包括rs140199800（SULT1C2，p=1.9×10-7），rs45580033(ASB2,p=4.2×10-10),和rs75426652(LHPP，p=7.2×10-14)，在调整了多重假设检验后。比较病例和对照的关联分析，以及包括母亲在内的模特，没有鉴定全基因组的显著变异。
结论：本研究发现了三种新的单核苷酸多态性，这些多态性与以前与神经管缺陷无关的生物学通路有关。该研究保证在更大的群体中复制，以验证研究结果并提供有针对性的预防策略。
方法：在本研究中，我们调查了跨越基因组的遗传变异与脊柱裂风险的关联(即，2016年12月至2022年12月在孟加拉国进行的一项病例对照研究中，招募了一部分家庭的脊髓膜膨出和脑膜膨出），在遗传研究中通常代表性不足的人群。使用Illumina全局筛选阵列分析唾液DNA样品。我们进行了遗传关联分析，以比较112例和121例对照儿童的等位基因频率。272位母亲128个三重奏
结果：在仅使用三重奏的传输不平衡测试分析中，我们确定了三个新的外显子脊柱裂风险位点，包括rs140199800（SULT1C2，p=1.9×10-7），rs45580033(ASB2,p=4.2×10-10),和rs75426652(LHPP，p=7.2×10-14)，在调整了多重假设检验后。比较病例和对照的关联分析，以及包括母亲在内的模特，没有鉴定全基因组的显著变异。
结论：本研究发现了三种新的单核苷酸多态性，这些多态性与以前与神经管缺陷无关的生物学通路有关。该研究保证在更大的群体中复制，以验证研究结果并提供有针对性的预防策略。
