Abstract:
BACKGROUND:In recent years, genome wide association studies have identified many genetic variants that are consistently associated with common complex diseases, but the amount of heritability explained by these risk alleles is still low. Part of the missing heritability may be due to genetic heterogeneity and small sample sizes, but non-optimal study designs in many genome wide association studies may also have contributed to the failure of identifying gene variants causing a predisposition to disease. The normally used odds ratio from a classical case-control study measures the association between genotype and being diseased. In comparison, under incidence density sampling, the incidence rate ratio measures the association between genotype and becoming diseased. We estimate the differences between the odds ratio and the incidence rate ratio under the presence of events precluding the disease of interest. Such events may arise due to pleiotropy and are known as competing events. In addition, we investigate how these differences impact the association test. METHODS:We simulate life spans of individuals whose gene variants are subject to competing events. To estimate the association between genotype and disease, we applied classical case-control studies and incidence density sampling. RESULTS:We find significant numerical differences between the odds ratio and the incidence rate ratio when the fact that gene variant may be associated with competing events, e.g. lifetime, is ignored. The only scenario showing little or no difference is an association with a rare disease and no other present associations. Furthermore, we find that p-values for association tests differed between the two study designs. CONCLUSIONS:If the interest is on the aetiology of the disease, a design based on incidence density sampling provides the preferred interpretation of the estimate. Under a classical case-control design and in the presence of competing events, the change in p-values in the association test may lead to false positive findings and, more importantly, false negative findings. The ranking of the SNPs according to p-values may differ between the two study designs.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Waltoft BL,Pedersen CB,Nyegaard M,Hobolth Adoi
10.1186/s12881-015-0210-1subject
Has Abstractpub_date
2015-08-30 00:00:00pages
71issn
1471-2350pii
10.1186/s12881-015-0210-1journal_volume
16pub_type
杂志文章abstract:BACKGROUND:Damaging variants in TRIO have been associated with moderate to severe neurodevelopmental disorders in humans. While recent work has delineated the positional effect of missense variation on the resulting phenotype, the clinical spectrum associated with loss-of-function variation has yet to be fully defined....
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01159-y
更新日期:2020-11-10 00:00:00
abstract:BACKGROUND:Ring chromosomes are one category of structurally abnormal chromosomes that can lead to severe growth retardation and other clinical defects. Traditionally, their diagnosis and characterization has largely relied on conventional cytogenetics and fluorescence in situ hybridization, array-based comparative gen...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0206-x
更新日期:2015-07-30 00:00:00
abstract:BACKGROUND:To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. METHODS:We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC. RESULTS:MUC2 mRNA were lower in HCC tissues (Mean -ΔCt = -4.70) than that in Non-HCC tissues (Mean -...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-14
更新日期:2013-01-25 00:00:00
abstract:BACKGROUND:Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in o...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-017-0474-8
更新日期:2017-10-16 00:00:00
abstract:BACKGROUND:Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast c...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-12
更新日期:2013-01-23 00:00:00
abstract:BACKGROUND:KCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann-Laband syndrome (ZLS). METHODS:Here, we report a new case of TMBTS diagnosed in a L...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0304-4
更新日期:2016-06-10 00:00:00
abstract:BACKGROUND:Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibrosis rema...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0324-0
更新日期:2016-09-05 00:00:00
abstract:BACKGROUND:Microspherophakia is a rare autosomal recessive eye disorder characterized by small spherical lens. It may present as an isolated finding or in association with other ocular and/or systemic disorders. This clinical and genetic heterogeneity requires the study of large genes (ADAMTSL4, FBN1, LTBP2, ADAMTSL-10...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0590-0
更新日期:2018-05-11 00:00:00
abstract:BACKGROUND:Congenital nystagmus (CN) and congenital cataracts are distinct eye diseases and are usually isolated. Cases with CN and congenital cataracts caused by different genes in one family have been rarely reported. CASE PRESENTATION:A 27-year-old man presented with CN and congenital cataracts and he underwent cat...
journal_title:BMC medical genetics
pub_type: 杂志文章,评审
doi:10.1186/s12881-019-0780-4
更新日期:2019-03-19 00:00:00
abstract:BACKGROUND:Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessiv...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-017-0404-9
更新日期:2017-05-03 00:00:00
abstract:BACKGROUND:Distal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders that involve multiple congenital limb contractures and comprise at least 10 clinical subtypes. Here, we describe our findings in two Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA. METHOD...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0692-8
更新日期:2018-10-03 00:00:00
abstract:BACKGROUND:Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR). HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-16
更新日期:2004-06-24 00:00:00
abstract::The Framingham Heart Study, founded in 1948 to examine the epidemiology of cardiovascular disease in a small town outside of Boston, has become the worldwide standard for cardiovascular epidemiology. It is among the longest running, most comprehensively characterized multi-generational studies in the world. Such semin...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-63
更新日期:2007-10-04 00:00:00
abstract:BACKGROUND:Many epidemiological studies have suggested that insulin-like growth factor1 (IGF1) gene single-nucleotide polymorphisms (SNPs) may be associated with cancer risk. Among several commonly studied polymorphisms in IGF1 gene, rs2195239 and rs2162679 attracted many attentions. So we perform a meta-analysis to de...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-019-0749-3
更新日期:2019-01-17 00:00:00
abstract:BACKGROUND:Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-39
更新日期:2008-05-06 00:00:00
abstract:BACKGROUND:The Krüppel-like factor (KLF) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-53
更新日期:2007-08-09 00:00:00
abstract:BACKGROUND:Epidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADI...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-014-0137-y
更新日期:2014-12-17 00:00:00
abstract:BACKGROUND:The platelet P2Y12 receptor plays a key role in platelet activation. The H2 haplotype of the P2Y12 receptor gene (P2RY12) has been found to be associated with maximal aggregation response to adenosine diphosphate (ADP) and with increased risk for peripheral arterial disease. No data are available on its asso...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-59
更新日期:2007-09-05 00:00:00
abstract:BACKGROUND:While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. METHODS:In this study, we report on clinica...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-0966-9
更新日期:2020-02-06 00:00:00
abstract:BACKGROUND:Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-49
更新日期:2010-03-30 00:00:00
abstract:BACKGROUND:Mutations in GATA6 are the most frequent cause of pancreatic agenesis. Most cases present with neonatal diabetes mellitus. CASE PRESENTATION:The case was a female born after an uncomplicated pregnancy and delivery in a non-consanguineous family (3.59 kg, 70th percentile). Severe cardiac malformations were d...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01012-2
更新日期:2020-04-03 00:00:00
abstract:BACKGROUND:Previous studies indicated a strong association between hyperkalemia and lung squamous cell carcinomas (LSCC). However, the underlying mechanism is not fully understood so far. METHODS:Literature-based data mining was conducted to identify genes, molecule, and cell processes linked to both hyperkalemia and ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01099-7
更新日期:2020-10-22 00:00:00
abstract:BACKGROUND:Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. OBJECTIVE:To investigate whether single nucleotide polymorphisms (SNPs) located ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-58
更新日期:2012-07-20 00:00:00
abstract:BACKGROUND:Germline genetic testing for familial cancer syndromes is usually performed serially for the most likely genetic causes. In recent years the way genetic testing carried out has changed, as next generation sequencing now allows the simultaneous testing of multiple susceptibility genes at low costs. CASE PRES...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-129
更新日期:2013-12-29 00:00:00
abstract:BACKGROUND:The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation. METHODS:The study population includes: 1123 healthy individuals, 100 homozyg...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-25
更新日期:2004-10-21 00:00:00
abstract:BACKGROUND:Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% o...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0361-8
更新日期:2016-12-13 00:00:00
abstract:BACKGROUND:Emerging evidence has shown that miRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in pre-miRNAs may affect the processing and therefore, influence the expression of mature miRNAs. Previous studies generated conflicting results when ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-119
更新日期:2012-12-10 00:00:00
abstract:BACKGROUND:Hearing loss is the most common sensory defect, and it affects over 6% of the population worldwide. Approximately 50-60% of hearing loss patients are attributed to genetic causes. Currently, more than 100 genes have been reported to cause non-syndromic hearing loss. It is possible and efficient to screen all...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01087-x
更新日期:2020-07-18 00:00:00
abstract:BACKGROUND:Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. METHODS:330 SNPs in 52 genes were studied in relation to plasma homocysteine ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-150
更新日期:2011-11-21 00:00:00
abstract:BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) has a major impact on the regulation of the folic acid pathway due to conversion of 5,10-methylenetetrahydrofolate (methylene-THF) to 5-methyl-THF. Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme act...
journal_title:BMC medical genetics
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2350-6-23
更新日期:2005-05-27 00:00:00