Genome-wide compound heterozygosity analysis highlighted 4 novel susceptibility loci for congenital heart disease in Chinese population

Clinical Genetics
T JiangZhibin Hu

Abstract

Genome-wide association studies (GWASs) have achieved great success in deciphering the genetic cause of congenital heart disease (CHD). However, the heritability of CHD remains to be clarified, and numerous genetic factors responsible for occurrence of CHD are yet unclear. In this study, we performed a genome-wide search for relaxed forms of compound heterozygosity (CH) in association with CHD using our existing GWAS data including 2265 individuals (957 CHD cases and 1308 controls). CollapsABEL was used to iteratively test the association between the CH genotype and the CHD phenotype in a sliding window manner. We highlighted 17 genetic loci showing suggestive CH-like associations with CHD (P < 5 × 10-8 ), among which 4 genetic loci had expression quantitative trait loci (eQTL) effects in blood (PeQTL  < 0.01). After conditional association analysis, each loci had only 1 independently effective signal reaching the significance threshold (rs2071477/rs3129299 at 6p21.32, P = 2.47 × 10-10 ; rs10773097/rs2880921 at 12q24.31, P = 3.30 × 10-8 ; rs73032040/rs7259476 at 19q13.11, P = 1.14 × 10-8 ; rs10416386/rs4239517 at 19q13.31, P = 1.15 × 10-9 ), together explained 7.83% of the CHD variance. Among these 4 associated loci, outstandin...Continue Reading

References

Aug 1, 1977·Tissue Antigens·W Mohl, W R Mayr
Jul 1, 1995·Circulation Research·L M Eisenberg, R R Markwald
Feb 17, 2001·The Journal of Investigative Dermatology·S SeiterM Zöller
Apr 1, 2003·IUBMB Life·Jacqueline M Matthews, Margaret Sunde
Apr 2, 2004·Pediatrics International : Official Journal of the Japan Pediatric Society·Shigetaka Katow
Dec 18, 2004·Human Immunology·Inna G OvsyannikovaGregory A Poland
Dec 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yuanyi FengChristopher A Walsh
Aug 21, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Line V HansenHelle Pappot
Oct 4, 2007·British Journal of Cancer·C ParetM Zöller
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
May 12, 2009·Nature Genetics·Jeffrey C BarrettUNKNOWN Type 1 Diabetes Genetics Consortium
Jun 23, 2010·Molecular Psychiatry·A DemirkanC M Middeldorp
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Oct 30, 2010·Traffic·Stéphanie Le BrasRoland Le Borgne
Dec 6, 2011·Nature Methods·Olivier DelaneauJean-François Zagury
Jun 21, 2012·Genetic Epidemiology·Sang Hong LeePeter M Visscher
Feb 16, 2013·Circulation Research·Akl C FahedChristine E Seidman
Feb 6, 2014·PLoS Genetics·Dennis J HazelettGerhard A Coetzee
May 13, 2014·Cell Reports·Xin-Xin I Zeng, Deborah Yelon
Oct 9, 2014·The Journal of Infectious Diseases·Nathaniel D LambertGregory A Poland
Feb 2, 2015·Cell Biochemistry and Biophysics·RongRong SunPeiying Zhang
Sep 21, 2016·The Journal of Investigative Dermatology·Kaiyin ZhongManfred Kayser

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Citations

Dec 27, 2019·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Shannon N Nees, Wendy K Chung
Dec 11, 2019·Cold Spring Harbor Perspectives in Biology·Shannon N Nees, Wendy K Chung
Oct 28, 2019·Birth Defects Research·Philip J LupoMary M Jenkins
Apr 9, 2021·Frontiers in Genetics·Dustin B Miller, Stephen R Piccolo

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