Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p=1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP(OR: 6.86, p=7.15 x 10-8), NR5A2(OR: 3.65, p=2.03 x 10-7) and MIR365-2(OR: 7.71, p=2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded novel candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection

BMC Medical Genetics ◽

10.1186/s12881-020-01156-1 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Sally N. Adebamowo ◽

◽

Adebowale A. Adeyemo ◽

Charles N. Rotimi ◽

Olayinka Olaniyan ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Association Study ◽

Genome Wide Association Study ◽

Principal Component ◽

Hpv Infection ◽

Genome Wide Association ◽

Replication Studies ◽

Genome Wide

Abstract Background Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10− 8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10− 6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10− 8), NR5A2 (OR: 3.65, p = 2.03 × 10− 7) and MIR365–2 (OR: 7.71, p = 2.63 × 10− 7) gene regions. Conclusions This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

10.21203/rs.2.16987/v2 ◽

2020 ◽

Author(s):

Sally N. Adebamowo ◽

Adebowale A Adeyemo ◽

Charles N Rotimi ◽

Olayinka Olaniyan ◽

Richard B. Offiong ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Association Study ◽

Genome Wide Association Study ◽

Principal Component ◽

Hpv Infection ◽

Genome Wide Association ◽

Replication Studies ◽

Genome Wide

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Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

10.21203/rs.2.16987/v4 ◽

2020 ◽

Author(s):

Sally N. Adebamowo ◽

Adebowale A Adeyemo ◽

Charles N Rotimi ◽

Olayinka Olaniyan ◽

Richard B. Offiong ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Association Study ◽

Genome Wide Association Study ◽

Principal Component ◽

Hpv Infection ◽

Genome Wide Association ◽

Replication Studies ◽

Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF 10 /LiPA 25 . hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10 -8 ). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p =1.43 x 10 -6 ). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p =7.15 x 10 -8 ), NR5A2 (OR: 3.65, p =2.03 x 10 -7 ) and MIR365-2 (OR: 7.71, p =2.63 x 10 -7 ) gene regions. Conclusions: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus (HPV) Infection

10.21203/rs.2.16987/v3 ◽

2020 ◽

Author(s):

Sally N. Adebamowo ◽

Adebowale A Adeyemo ◽

Charles N Rotimi ◽

Olayinka Olaniyan ◽

Richard B. Offiong ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Association Study ◽

Genome Wide Association Study ◽

Principal Component ◽

Hpv Infection ◽

Genome Wide Association ◽

Replication Studies ◽

Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes.Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10-8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p =1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p =7.15 x 10-8), NR5A2 (OR: 3.65, p =2.03 x 10-7) and MIR365-2 (OR: 7.71, p =2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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Association of JAG1 with Bone Mineral Density and Osteoporotic Fractures: A Genome-wide Association Study and Follow-up Replication Studies

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2009.12.014 ◽

2010 ◽

Vol 86 (2) ◽

pp. 229-239 ◽

Cited By ~ 146

Author(s):

Annie W.C. Kung ◽

Su-Mei Xiao ◽

Stacey Cherny ◽

Gloria H.Y. Li ◽

Yi Gao ◽

...

Keyword(s):

Bone Mineral Density ◽

Association Study ◽

Genome Wide Association Study ◽

Osteoporotic Fractures ◽

Genome Wide Association ◽

Mineral Density ◽

Replication Studies ◽

Genome Wide ◽

A Genome

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Identification of genetic factors controlling phosphorus utilization efficiency in wheat by genome-wide association study with principal component analysis

10.1101/2020.09.04.283556 ◽

2020 ◽

Author(s):

Luqman Bin Safdar ◽

Muhammad Jawad Umer ◽

Fakhrah Almas ◽

Siraj Uddin ◽

Qurra-tul-Ain Safdar ◽

...

Keyword(s):

Association Study ◽

Candidate Genes ◽

Genetic Factors ◽

Genome Wide Association Study ◽

Principal Component ◽

Utilization Efficiency ◽

Genome Wide Association ◽

Genome Wide ◽

P Utilization ◽

P Utilization Efficiency

ABSTRACTDespite the economic importance of P utilization efficiency, information on genetic factors underlying this trait remains elusive. To address that, we performed a genome-wide association study in a spring wheat diversity panel ranging from landraces to elite varieties. We evaluated the phenotype variation for P utilization efficiency in controlled conditions and genotype variation using wheat 90K SNP array. Phenotype variables were transformed into a smaller set of uncorrelated principal components that captured the most important variation data. We identified two significant loci associated with both P utilization efficiency and the 1st principal component on chromosomes 3A and 4A: qPE1-3A and qPE2-4A. Annotation of genes at these loci revealed 53 wheat genes, among which 6 were identified in significantly enriched pathways. The expression pattern of these 6 genes indicated that TraesCS4A02G481800, involved in pyruvate metabolism and TCA cycle, had a significantly higher expression in the P efficient variety under limited P conditions. Further characterization of these loci and candidate genes can help stimulate P utilization efficiency in wheat.KEY MESSAGEWe report two new loci for P utilization efficiency on chromosomes 3A and 4A of wheat. The prioritized candidate genes at these loci can be investigated by molecular biology techniques to improve P efficiency in wheat and grass relatives.

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Genome-Wide Association Study for Coronary Artery Calcification With Follow-Up in Myocardial Infarction

Circulation ◽

10.1161/circulationaha.110.974899 ◽

2011 ◽

Vol 124 (25) ◽

pp. 2855-2864 ◽

Cited By ~ 196

Author(s):

Christopher J. O'Donnell ◽

Maryam Kavousi ◽

Albert V. Smith ◽

Sharon L.R. Kardia ◽

Mary F. Feitosa ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Association Study ◽

Coronary Artery Calcification ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide

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Erratum: Multiple-trait genome-wide association study based on principal component analysis for residual covariance matrix

Heredity ◽

10.1038/hdy.2015.11 ◽

2015 ◽

Vol 114 (4) ◽

pp. 428-428 ◽

Cited By ~ 1

Author(s):

H Gao ◽

Y Wu ◽

T Zhang ◽

Y Wu ◽

L Jiang ◽

...

Keyword(s):

Principal Component Analysis ◽

Association Study ◽

Covariance Matrix ◽

Genome Wide Association Study ◽

Principal Component ◽

Component Analysis ◽

Genome Wide Association ◽

Multiple Trait ◽

Genome Wide ◽

Residual Covariance

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Genome-wide association study of response to cognitive–behavioural therapy in children with anxiety disorders

The British Journal of Psychiatry ◽

10.1192/bjp.bp.115.168229 ◽

2016 ◽

Vol 209 (3) ◽

pp. 236-243 ◽

Cited By ~ 18

Author(s):

Jonathan R. I. Coleman ◽

Kathryn J. Lester ◽

Robert Keers ◽

Susanna Roberts ◽

Charles Curtis ◽

...

Keyword(s):

Anxiety Disorders ◽

Association Study ◽

Treatment Response ◽

Genome Wide Association Study ◽

Behavioural Therapy ◽

Post Treatment ◽

Genome Wide Association ◽

Genome Wide ◽

Cognitive Behavioural

BackgroundAnxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.AimsTo perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).MethodPresence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.ResultsNo variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.ConclusionsThis is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

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Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes

Multiple Sclerosis Journal ◽

10.1177/1352458511432741 ◽

2011 ◽

Vol 18 (7) ◽

pp. 959-965 ◽

Cited By ~ 20

Author(s):

Jezabel Varadé ◽

Manuel Comabella ◽

Miguel A Ortiz ◽

Rafael Arroyo ◽

Oscar Fernández ◽

...

Keyword(s):

Multiple Sclerosis ◽

Autoimmune Diseases ◽

Association Study ◽

Genome Wide Association Study ◽

Susceptibility Gene ◽

Pooled Analysis ◽

Replication Study ◽

Genome Wide Association ◽

Genome Wide

Background and objectives: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. Methods: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. Results: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). Conclusions: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: pM-H=0.001; ORM-H (95% CI)= 0.84 (0.75–0.93)], IL12B [rs6887695: pM-H=0.03; ORM-H (95% CI)= 1.09 (1.01–1.17)] and CBLB [rs9657904: pM-H=0.01; ORM-H (95% CI)= 0.89 (0.81–0.97)].

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