Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

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The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.


We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were used. Premature infants and mothers of premature infants were defined as affected cases in independent analyses.


Analyses with the infant as the case identified two genes with evidence of linkage: CRHR1 (P = 0.0012) and CYP2E1 (P = 0.0011). Analyses with the mother as the case identified four genes with evidence of linkage: ENPP1 (P = 0.003), IGFBP3 (P = 0.006), DHCR7 (P = 0.009), and TRAF2 (P = 0.01). DNA sequence analysis of the coding exons and splice sites for CRHR1 and TRAF2 identified no new likely etiologic variants.


These findings suggest the involvement of six genes acting through the infant and/or the mother in the etiology of PTB.

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The authors thank all the families participating in the study as well as the staff responsible for obtaining consent and samples from participants, in particular, Laura Knosp, Sarah Wente, Gretchen Cress, Ruthann Schrock, Sara Scott, and Nancy Krutzfield at the University of Iowa; Karen Debes at the Magee Womens Hospital; Lauren Smith and Eileen Blakely at the University of Rochester; Kristi Lanier at the Wake Forest University; and Dorthe Grosen and Bibi Anshoj at the University of Southern Denmark. Susan Berends helped to identify extended families and Dina Ahram provided student support in the lab.

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Correspondence to Jeffrey C. Murray.

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