Aschebrook-Kilfoy Briseis, Argos Maria, Pierce Brandon L, Tong Lin, Jasmine Farzana, Roy Shantanu, Parvez Faruque, Ahmed Alauddin, Islam Tariqul, Kibriya Muhammad G, Ahsan Habibul
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America; Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, United States of America.
PLoS One. 2015 Mar 5;10(3):e0118488. doi: 10.1371/journal.pone.0118488. eCollection 2015.
Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10(-7) and number of pregnancies at P <10(-6). This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10(-6). The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10(-5) for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis.
人类生育能力是一种复杂性状，由基因与环境的相互作用决定，其中遗传因素是一个重要组成部分。为了更好地理解生育能力的个体间差异，我们开展了针对常见生育表型、终身怀孕次数以及一个发展中国家人口中子女数量的首批全基因组关联研究（GWAS）之一。生育表型数据和DNA样本是在基线招募时从参与孟加拉国一项大型前瞻性队列研究的个体中获取的。在1686名已婚女性中进行了生育表型的GWAS分析。4号染色体上的一个单核苷酸多态性（SNP）与子女数量在P<10⁻⁷时、怀孕次数在P<10⁻⁶时呈非显著关联。该SNP位于1兆碱基（Mb）范围内无基因的区域。6号染色体上的一个SNP与子女数量极端值在P<10⁻⁶时呈非显著关联。与该SNP距离最近的基因是HDGFL1，一种肝癌衍生生长因子。当我们排除使用激素避孕的人群后，5号染色体上的一个SNP与子女数量和怀孕次数在P<10⁻⁵时呈非显著关联。该SNP位于C5orf64（一个开放阅读框）和ZSWIM6（一个锌离子结合基因）附近。我们还使用全基因组复杂性状分析（GCTA）从我们的基因型数据中估计了这些表型的遗传力，子女数量的遗传力（hg² = 0.149，标准误 = 0.24，p值 = 0.265）以及怀孕次数的遗传力（hg² = 0.007，标准误 = 0.22，p值 = 0.487）。我们在孟加拉国进行的全基因组关联研究以及对怀孕次数和子女数量的遗传力估计，并未为胎次变异的常见变异提供有力证据。然而，我们的结果表明，未来的研究在分析中可能需要考虑3个显著SNP的作用。
