Browsing by Author "Khan, Raiyan R."

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    Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas
    (Springer Nature, 2024-05-07) Khan, Raiyan R.; Guerrero, Rafael F.; Wapner, Ronald J.; Hahn, Matthew W.; Raja, Anita; Salleb‑Aouissi, Ansaf; Grobman, William A.; Simhan, Hyagriv; Silver, Robert M.; Chung, Judith H.; Reddy, Uma M.; Radivojac, Predrag; Pe’er, Itsik; Haas, David M.; Obstetrics and Gynecology, School of Medicine
    Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.
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    Polygenic prediction of preeclampsia and gestational hypertension
    (Springer Nature, 2023) Honigberg, Michael C.; Truong, Buu; Khan, Raiyan R.; Xiao, Brenda; Bhatta, Laxmi; Vy, Ha My T.; Guerrero, Rafael F.; Schuermans, Art; Selvaraj, Margaret Sunitha; Patel, Aniruddh P.; Koyama, Satoshi; Cho, So Mi Jemma; Vellarikkal, Shamsudheen Karuthedath; Trinder, Mark; Urbut, Sarah M.; Gray, Kathryn J.; Brumpton, Ben M.; Patil, Snehal; Zöllner, Sebastian; Antopia, Mariah C.; Saxena, Richa; Nadkarni, Girish N.; Do, Ron; Yan, Qi; Pe’er, Itsik; Verma, Shefali Setia; Gupta, Rajat M.; Haas, David M.; Martin, Hilary C.; van Heel, David A.; Laisk, Triin; Natarajan, Pradeep; Obstetrics and Gynecology, School of Medicine
    Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.
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    Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b
    (Oxford University Press, 2023) Yan, Qi; Guerrero, Rafael F.; Khan, Raiyan R.; Surujnarine, Andy A.; Wapner, Ronald J.; Hahn, Matthew W.; Raja, Anita; Salleb-Aouissi, Ansaf; Grobman, William A.; Simhan, Hyagriv; Blue, Nathan R.; Silver, Robert; Chung, Judith H.; Reddy, Uma M.; Radivojac, Predrag; Pe’er, Itsik; Haas, David M.; Obstetrics and Gynecology, School of Medicine
    Adverse pregnancy outcomes (APOs) are major risk factors for women's health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWASs) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display extensive results, we developed a web-based tool GnuMoM2b (https://gnumom2b.cumcobgyn.org/) for searching, visualizing, and sharing results from a GWAS of 479 pregnancy traits as well as phenome-wide association studies of more than 17 million single nucleotide polymorphisms. The genetic results from 3 ancestries (Europeans, Africans, and Admixed Americans) and meta-analyses are populated in GnuMoM2b. In conclusion, GnuMoM2b is a valuable resource for extraction of pregnancy-related genetic results and shows the potential to facilitate meaningful discoveries.