Genome-wide association study of parity in Bangladeshi women.
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.
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Briseis
B
Aschebrook-Kilfoy
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Maria
M
Argos
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.
Brandon L
BL
Pierce
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Lin
L
Tong
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Farzana
F
Jasmine
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Shantanu
S
Roy
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
Faruque
F
Parvez
UChicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
Alauddin
A
Ahmed
UChicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
Tariqul
T
Islam
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America.
Muhammad G
MG
Kibriya
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; Departments of Medicine and Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Habibul
H
Ahsan
D000328:Adult; D001459:Bangladesh; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010298:Parity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci