Replication of GWAS loci revealed the moderate effect of <i>TNRC6B</i> locus on susceptibility of Saudi women to develop uterine leiomyomas

Bondagji, Nabeel S.; Morad, Fatima A.; Al-Nefaei, Afnan Abed Abdullah; Khan, Imran Ali; Elango, Ramu; Abdullah, Layla S.; Almansouri, Nisma; Sabir, Jamal S. M.; Edris, Sherif; Shaik, Noor Ahmad

doi:10.1111/jog.13217

Cited by 16 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our multi-ethnic replication implies that the discovered loci are indeed involved in UL development, and the early UL association studies have likely been underpowered to detect them. Three previously reported loci, at OBFC1 ( Cha et al, 2011 ), TNRC6B ( Cha et al, 2011 ; Edwards et al, 2013a ; Aissani et al, 2015 ; Bondagji et al, 2017 ) and BET1L ( Cha et al, 2011 ; Edwards et al, 2013b ), were also validated, however, the mechanistic connection to UL development remains obscure for the latter two.…”

Section: Discussionmentioning

confidence: 86%

“…The 11p15.5 locus - near the Bet1 golgi vesicular membrane trafficking protein like ( BET1L ) gene - was later replicated in Caucasian ancestry ( Edwards et al, 2013a ). The 22q13.1 locus has been replicated in Caucasian, American and Saudi Arabian populations suggesting trinucleotide repeat containing 6B ( TNRC6B ) as a possible target gene ( Edwards et al, 2013a ; Aissani et al, 2015 ; Bondagji et al, 2017 ). Further UL predisposition loci have been suggested at 1q42.2 and 2q32.2 by Zhang et al ( Zhang et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

Välimäki

Kuisma

Pasanen

et al. 2018

eLife

View full text Add to dashboard Cite

Uterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting the role of telomere maintenance - TP53 and ATM. Genes involved in genitourinary development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem cell marker antigen CD44, formed another strong subgroup. The combined risk contributed by the 22 loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

Välimäki

Kuisma

Pasanen

et al. 2018

eLife

View full text Add to dashboard Cite

show abstract

“…However, Bondagji et al . performed a replication study based on Saudi women, and rs2280543 from BET1L was not reported to be significant 16 . This difference might be due to the different LD structures from different genetic backgrounds.…”

Section: Discussionmentioning

confidence: 98%

“…These three loci included several genes such as STE20 Like Kinase ( SLK ), Oligosaccharide-Binding Fold-Containing Protein 1 (OBFC1), Trinucleotide Repeat Containing 6B ( TNRC6B ), Outer Dense Fiber 3 ( ODF3 ), Bet1 Golgi Vesicular Membrane Trafficking Protein Like ( BET1L ), RIC8 Guanine Nucleotide Exchange Factor A ( RIC8A ), and Sirtuin 3 ( SIRT3 ). Since then, several follow up studies have tried to replicate these initial GWAS findings using study samples based on other ethnic groups 14 – 16 . However, the results of these subsequent studies have not been concordant and have, at times, been contradictory.…”

Section: Introductionmentioning

confidence: 99%

Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population

Liu

Jiang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Previous studies have shown that uterine leiomyomas (UL) are benign tumours with contributions from environmental and genetic factors. We aimed to replicate two initial significant genetic factors, TNRC6B and BET1L, in a Han Chinese population. A total of 2,055 study subjects were recruited, and 55 SNPs mapped to TNRC6B and BET1L were selected and genotyped in samples from these subjects. Genetic associations were analysed at both the single marker and haplotype levels. Associations between targeted SNPs and relevant clinical features of UL were analysed in case only samples. Functional consequences of significant SNPs were analysed by bioinformatics tools. Two SNPs, rs2280543 from BET1L (χ2 = 18.3, OR = 0.64, P = 1.87 × 10−5) and rs12484776 from TNRC6B (χ2 = 19.7, OR = 1.40, P = 8.91 × 10−6), were identified as significantly associated with the disease status of UL. Rs2280543 was significantly associated with the number of fibroid nodes (P = 0.0007), while rs12484776 was significantly associated with node size (χ2 = 54.88, P = 3.44 × 10−11). Both SNPs were a significant eQTL for their genes. In this study, we have shown that both BET1L and TNRC6B contributed to the risk of UL in Chinese women. Significant SNPs from BET1L and TNRC6B were also identified as significantly associated with the number of fibroid nodes and the size of the node, respectively.

show abstract

“…Advances in sequencing technologies, particularly, high throughput sequencing have permitted the discovery of novel genes responsible for cancer heritability, facilitating efficient genetic screening. [14][15][16] The major genetic changes in cancer include single nucleotide variants (SNVs); duplications, insertions, or deletions; exon and gene copy number changes; and structural variants (SVs). 17 The molecular profiling of heritable cancer genes ranges from simple assessments of known hotspot mutations in single genes, to more complex tests that simultaneously detect all gene alterations using allele-specific PCR, Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), pyrosequencing or mass spectrometry (MS).…”

Section: Introductionmentioning

confidence: 99%

Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

et al. 2020

View full text Add to dashboard Cite

The study of hereditary cancer, which accounts for~10% of cancer cases worldwide is an important subfield of oncology. Our understanding of hereditary cancers has greatly advanced with recent advances in sequencing technology, but as with any genetic trait, gene frequencies of cancer-associated mutations vary across populations, and most studies that have located hereditary cancer genes have been conducted on European or Asian populations. There is an urgent need to trace hereditary cancer genes across the Arab world. Hereditary disease is particularly prevalent among members of consanguineous populations, and consanguineous marriages are particularly common in the Arab world. There are also cultural and educational idiosyncrasies that differentiate Arab populations from other more thoroughly studied groups with respect to cancer awareness and treatment. Therefore, a review of the literature on hereditary cancers in this understudied population was undertaken. We report that BRCA mutations are not as prevalent among Arab breast cancer patients as they are among other ethnic groups, and therefore, other genes may play a more important role. A wide variety of germline inherited mutations that are associated with cancer are discussed, with particular attention to breast, ovarian, colorectal, prostate, and brain cancers. Finally, we describe the state of the profession of familial cancer genetic counselling in the Arab world, and the clinics and societies dedicated to its advances. We describe the complexities of genetic counselling that are specific to the Arab world. Understanding hereditary cancer is heavily dependent on understanding population-specific variations in cancer-associated gene frequencies.

show abstract

Replication of GWAS loci revealed the moderate effect of TNRC6B locus on susceptibility of Saudi women to develop uterine leiomyomas

Cited by 16 publications

References 49 publications

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population

Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

Contact Info

Product

Resources

About