Germline copy number variants and endometrial cancer risk DOI Creative Commons

Cassie E. Stylianou,

George A. R. Wiggins,

V. Lau

et al.

Human Genetics, Journal Year: 2024, Volume and Issue: 143(12), P. 1481 - 1498

Published: Nov. 4, 2024

Abstract Known risk loci for endometrial cancer explain approximately one third of familial cancer. However, the association germline copy number variants (CNVs) with remains relatively unknown. We conducted a genome-wide analysis rare CNVs overlapping gene regions in 4115 cases and 17,818 controls to identify functionally relevant associated disease. identified 1.22-fold greater DNA samples from compared ( p = 4.4 × 10 –63 ). Under three models putative CNV impact (deletion, duplication, loss function), studies 141 candidate < 0.01) risk. Pathway revealed an enrichment genes involved 16p11.2 proximal deletion syndrome, driven by large recurrent (chr16:29,595,483-30,159,693) 0.15% 0.02% control participants. Together, these data provide evidence that have role susceptibility BP4-BP5 region contains 25 gene(s) warrant further better understand their human

Language: Английский

The pleiotropic spectrum of proximal 16p11.2 CNVs DOI Creative Commons
Chiara Auwerx, Zoltán Kutalik, Alexandre Reymond

et al.

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

3
Genetic modifiers and ascertainment drive variable expressivity of complex disorders DOI Creative Commons
Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

SUMMARY Variable expressivity of disease-associated variants implies a role for secondary that modify clinical features. We assessed the effects modifier towards outcomes 2,252 individuals with primary variants. Among 132 families 16p12.1 deletion, distinct rare and common variant classes conferred risk specific developmental features, including short tandem repeats neurological defects SNVs microcephaly, while additional multiple genetic diagnoses. Within disease population cohorts 773 we found opposing features across ascertainments. Additional analysis 1,479 probands other variants, such as 16p11.2 deletion CHD8 1,084 without showed phenotypic associations differed by context were influenced synergistic interactions between Our study provides paradigm to dissect genomic architecture complex disorders personalized treatment.

Language: Английский

Citations

2
Germline copy number variants and endometrial cancer risk DOI Creative Commons

Cassie E. Stylianou,

George A. R. Wiggins,

V. Lau

et al.

Human Genetics, Journal Year: 2024, Volume and Issue: 143(12), P. 1481 - 1498

Published: Nov. 4, 2024

Abstract Known risk loci for endometrial cancer explain approximately one third of familial cancer. However, the association germline copy number variants (CNVs) with remains relatively unknown. We conducted a genome-wide analysis rare CNVs overlapping gene regions in 4115 cases and 17,818 controls to identify functionally relevant associated disease. identified 1.22-fold greater DNA samples from compared ( p = 4.4 × 10 –63 ). Under three models putative CNV impact (deletion, duplication, loss function), studies 141 candidate < 0.01) risk. Pathway revealed an enrichment genes involved 16p11.2 proximal deletion syndrome, driven by large recurrent (chr16:29,595,483-30,159,693) 0.15% 0.02% control participants. Together, these data provide evidence that have role susceptibility BP4-BP5 region contains 25 gene(s) warrant further better understand their human

Language: Английский

Citations

0