Recurrence Risk Ratio Research Articles

Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia.

Magnesium sulphate remains the drug of choice for both prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but have not yet been formally evaluated. To assess the comparative effects of alternative regimens for the administration of magnesium sulphate when used for the care of women with pre-eclampsia or eclampsia, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2010). Randomised trials comparing different regimens for administration of magnesium sulphate used for the care of women with pre-eclampsia or eclampsia, or both. All four review authors assessed trial quality and extracted data independently. We identified 17 studies of which six (866 women) met the inclusion criteria: two trials (451 women) compared regimens for women with eclampsia and four (415 women) for women with pre-eclampsia.Treatment of eclampsia: one trial compared loading dose alone with loading dose plus maintenance therapy for 24 hours (401 women). There was no clear difference between the groups in the risk ratio (RR) of recurrence of convulsions (RR 1.13, 95% confidence interval (CI) 0.42 to 3.05) or stillbirth (RR 1.13, 95% CI 0.66 to 1.92), and the CIs are wide. One trial compared a low dose regimen with a standard dose regimen over 24 hours (50 women). This study was too small for any reliable conclusions about the comparative effects.Prevention of eclampsia: one trial compared intravenous with intramuscular maintenance regimen for 24 hours (17 women). This trial was too small for any reliable conclusions. Three trials compared short maintenance regimens postpartum with continuing for 24 hours after the birth (398 women), even taken together these trials were too small for any reliable conclusions. Although strong evidence supports the use of magnesium sulphate for prevention and treatment of eclampsia, trials comparing alternative treatment regimens are too small for reliable conclusions.

Heritability of audiometric shape parameters and familial aggregation of presbycusis in an elderly Flemish population

This study describes the heritability of audiometric shape parameters and the familial aggregation of different types of presbycusis in a healthy, otologically screened population between 50 and 75 years old. About 342 siblings of 64 families (average family-size: 5.3) were recruited through population registries. Audiometric shape was mathematically quantified by objective parameters developed to measure size, slope, concavity, percentage of frequency-dependent and frequency-independent hearing loss and Bulge Depth. The heritability of each parameter was calculated using a variance components model. Logistic regression models were used to estimate the odds ratios (ORs). Estimates of sibling recurrence risk ratios ( λ s ) are also provided. Heritability estimates were generally higher compared to previous studies. ORs and λ s for the parameters Total Hearing Loss (size), Uniform Hearing Loss (percentage of frequency-dependent hearing loss) and Bulge Depth suggest a higher heredity for severe types of presbycusis compared to moderate or mild types. Our results suggest that the separation of the parameter ‘Total Hearing Loss’ into the two parameters ‘Uniform Hearing Loss’ and ‘Non-uniform Hearing Loss’ could lead to the discovery of different genetic subtypes of presbycusis. The parameter ‘Bulge Depth’, instead of ‘Concavity’, seemed to be an important parameter for classifying subjects into ‘susceptible’ or ‘resistant’ to societal or intensive environmental exposure.

Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer

Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer. The rare allele of FAS 1377G>A was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377G>A (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592C>A polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592C>A polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677C>T, VEGF 936C>T, CCND1 870G>A, TGFB1 29T>C, FASLG 844C>T, FAS 670A>G, GPB3 825C>T, ITGA2 807C>T, ITGA2 1648G>A, ITGB3 176T>C, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473T>C, IL10 592C>A and SULT1A1 638G>A polymorphisms and disease-free survival or overall survival. Our data suggest that the FAS 1377G>A and IL10 592C>A polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.

Mexican-American Admixture Mapping Analyses for Diabetic Nephropathy in Type 2 Diabetes Mellitus

Diabetic nephropathy is a classic complex trait, whose development in a given individual reflects contributions from multiple genes and whose expression is modulated by environmental factors. Numerous genetic strategies have been used to identify common disease risk loci and genes, including candidate gene analyses, linkage analysis, transmission disequilibrium testing (a family based association test to identify linkage between a genetic marker and a biological trait or disease), and admixture mapping (also referred to as mapping by admixture linkage disequilibrium). Choosing the best genetic strategy to identify susceptibility genes in a disease is dependent on knowing whether the disorder is monogenic (the result of one gene), oligogenic (the result of a few genes), or polygenic (the result of many genes). The likelihood of finding risk loci for a disease with a putative genetic contribution is in part owing to the disease recurrence risk ratio (the risk of expressing the disease phenotype in siblings of the proband divided by the risk observed in the general population), the genotypic risk ratio (the risk of expressing the phenotype if the gene is present divided by the risk if the gene is not present), the number of susceptibility genes, how the susceptibility genes interact, how much of the disease risk is contributed by environmental factors, and the disease penetrance (the likelihood that the phenotype will be expressed if the gene is present).

Changes of exercise and the clinical effects among eldly non-small cell lung cancer survivors

背景与目的运动对健康有重要影响，可以提高癌症生存者的心血管系统功能、肌力和幸福感等，并减少乏力、焦虑、抑郁等。但目前关于肺癌患者治疗后运动能力的改变及其与肿瘤复发的关系目前尚不明了。本研究拟探讨老年非小细胞肺癌生存者体能锻炼行为模式的改变和临床意义。方法采用回顾分析方法，调查包括手术后、化放疗后病情稳定者和服用酪氨酸激酶抑制剂行靶向治疗的老年肺癌生存者，记录其诊断前、积极治疗3个月和1年的运动量和每周运动频率，了解患者运动动机和偏好，探讨运动与肿瘤复发的关系。结果调查了58例老年肺癌生存者，发现治疗期间老年肺癌生存者的体能锻炼参与比例下降，但1年后平均轻度体力活动较治疗前有增加。1年后运动基本达标的患者占75.9%（44/58），肺癌复发/进展率为20.0%（7/35），不达标的患者占24.1%（14/58），复发/进展率为35.7%（5/14），运动不达标时肿瘤复发/进展的风险比（risk ratio, RR）为2.14（95%CI:0.81-5.68, P=0.26）。肿瘤生存者运动的动机主要有改善健康、增加体能，维持正常生活方式、增加免疫力等，而最常见的障碍是疲乏、不舒服和缺少动机等。结论治疗期间老年肺癌生存者的体能锻炼参与比例降到原有的10%以下，而且即便是治疗完成后也不能恢复到诊断前的水平，运动不达标时和运动达标时患者肿瘤复发/进展的情况无明显差异，运动与肿瘤复发的关系有待进一步研究。

LACK OF REPLICATION OF ASSOCIATION BETWEEN SCN1A SNP AND FEBRILE SEIZURES

Febrile seizures (FS) affect 3% of children aged 6 months to 6 years and have a strong genetic component with recurrence risk ratios of 3–5 in first-degree relatives.1 In rare families with autosomal dominant FS, mutations in the sodium channel alpha 1 subunit gene, SCN1A , have been identified.2,3 However, FS usually show complex inheritance with a polygenic basis. The search for susceptibility variants has been slow, so the recent report of a common splice site single nucleotide polymorphism (SNP) in SCN1A (IVS5N + 5 G>A, rs3812718) is notable. Two patient groups were studied: the first, adults with focal epilepsy with and without a history of FS (n = 90 and 486 respectively); the second, children with FS (n = 144). Patients homozygous for the A allele were reported to have a genotype relative risk of ∼3.0 for FS.4 The rs3812718 SNP is a plausible candidate for FS as it influences relative expression of neonatal and adult transcripts of SCN1A , which plays a key role in membrane excitability.5 To confirm the association between rs3812718 and FS, independent replication studies are vital.6 We tested the primary hypothesis of the original study, that an AA genotype at this SCN1A polymorphism confers increased risk of FS. For this, we recruited 558 unrelated Australian (predominantly Caucasian) patients from epilepsy clinics at 2 tertiary hospitals in Melbourne. The criteria for a diagnosis of FS were identical to that of the original study. Patients with an afebrile seizure history prior to the onset of FS were excluded. The genotyping methodology has been described previously.7 Approval was obtained from the Human Research Ethics Committees of Austin and Melbourne Health. The cohort of 558 patients comprised 76 (14%) cases with and 482 (86%) without a history of FS. A total of …

Increased Risk of Complex Regional Pain Syndrome in Siblings of Patients?

An increased risk among siblings of probands with complex regional pain syndrome (CRPS) may be indicative of a genetic contribution. We calculated the sibling recurrence risk ratio (lambda(sibling)), a measure of familial aggregation. We surveyed 405 CRPS patients to collect information on the occurrence of CRPS in their siblings and compared this risk with the population risk to develop the syndrome. Information on disease status was collected from 1242 siblings, of which 24 were possibly affected according to their siblings. The diagnosis was confirmed in 16 patients, rejected in 2, and could not be verified in the remaining 6. Age-specific risk ratios were calculated for younger (<50 years) and older (> or =50 years) age groups. The strongest effects were seen in the younger age group, with a lambda(sibling) for possibly affected and confirmed cases of 5.6 (95% CI, 3.0 to 9.8) and 3.4 (95% CI, 1.5 to 6.8), respectively. We concluded that this study yielded no indications for an overall increased risk of developing CRPS for siblings of CRPS patients but that the risk was significantly increased in siblings younger than 50, which may indicate that genetic factors play a more pronounced role in this subgroup. We studied the risk of developing CRPS for siblings of patients with this syndrome. Although the overall risk for siblings was not increased compared with the population risk, the risk for younger siblings was elevated. To enhance chances of success, future genetic studies may consider restricting inclusion to younger-onset cases.

A Population-Based Study of Australian Twins with Melanoma Suggests a Strong Genetic Contribution to Liability

Melanoma runs within families, but this may be due to either shared genetic or shared environmental influences within those families. The concordance between pairs of non-identical twins compared to that between identical twins can be used to determine whether familial aggregation is due to genetic or environmental factors. Mandatory reporting of melanoma cases in the state of Queensland yielded approximately 12,000 cases between 1982 and 1990. Twins in this study and from the adjacent state of New South Wales (125 pairs in total) were used to partition variation in liability to melanoma into genetic and environmental factors. Identical twins were more concordant for melanoma (4 of 27 pairs) than non-identical twins (3 of 98 pairs; P-value approximately 0.04). Identical co-twins of affected individuals were 9.8 times more likely to be affected than by chance. However, non-identical co-twins of affected individuals were only 1.8 times more likely to be affected than by chance. An MZ:DZ recurrence risk ratio of 5.6 suggests that some of the genetic influences on melanoma are due to epistatic (gene-gene) interactions. Using these data and population prevalences, it was estimated that 55% of the variation in liability to melanoma is due to genetic influences.

Recurrence of Congenital Heart Defects in Families

Knowledge of the familial contribution to congenital heart diseases (CHD) on an individual and population level is sparse. We estimated an individual's risk of CHD given a family history of CHD, as well as the contribution of CHD family history to the total number of CHD cases in the population. In a national cohort study, we linked all Danish residents to the National Patient Register, the Causes of Death Register, the Danish Central Cytogenetic Register, and the Danish Family Relations Database, yielding 1 763 591 persons born in Denmark between 1977 and 2005, of whom 18 708 had CHD. Individuals with CHD were classified by phenotype. We estimated recurrence risk ratios and population-attributable risk. Among first-degree relatives, the recurrence risk ratio was 79.1 (95% confidence interval [CI] 32.9 to 190) for heterotaxia, 11.7 (95% CI, 8.0 to 17.0) for conotruncal defects, 24.3 (95% CI,12.2 to 48.7) for atrioventricular septal defect, 12.9 (95% CI, 7.48 to 22.2) for left ventricular outflow tract obstruction, 48.6 (95% CI, 27.5 to 85.6) for right ventricular outflow tract obstruction, 7.1 (95% CI, 4.5 to 11.1) for isolated atrial septal defect, and 3.4 (95% CI, 2.2 to 5.3) for isolated ventricular septal defect. The overall recurrence risk ratio for the same defect was 8.15 (95% CI, 6.95 to 9.55), whereas it was 2.68 (95% CI, 2.43 to 2.97) for different heart defects. Only 2.2% of heart defect cases in the population (4.2% after the exclusion of chromosomal aberrations) were attributed to CHD family history in first-degree relatives. Specific CHDs showed highly variable but strong familial clustering in first-degree relatives, ranging from 3-fold to 80-fold compared with the population prevalence, whereas the crossover risks between dissimilar cases of CHD were weaker. Family history of any CHD among first-degree relatives accounted for a small proportion of CHD cases in the population.

Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery

4090 Background: To investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection. Methods: Patients with Stage II or Stage III colorectal cancer (CRC) were randomly assigned to receive preoperative hepatic and regional arterial chemotherapy (PHRAC group, n=256) or surgery alone (control group, n=253). The primary endpoint was disease-free survival, whereas the secondary endpoints included liver metastasis-free survival and overall survival. Results: There were no significant differences in overall morbidity between PHRAC and Control groups. During the follow-up period (median, 42 months), the median liver metastasis time for patients with stage III CRC was significantly longer in the PHRAC group (16±3 months v.s. 8±1 months, P=0.01). In stage III patients, there was also significant difference between the two groups with regard to the incidence of liver metastasis (18.9% vs 27.3%, P=0.01), 5-year disease-free survival (70.2% vs 52.0%, P=0.0076), 5-year overall survival (80.3% vs 69.5%, P=0.020) and the median survival time (40.1± 4.6 months vs 36.3 ± 3.2 months, P=0.03). In the PHRAC arm, the risk ratio of recurrence was 0.63 (95% CI, 0.51–0.79, P=0.0001), of death was 0.50(95% CI, 0.32–0.67; P=0.005), and of liver metastasis was 0.70 (95% CI, 0.52–0.86; p=0.01). In contrast, PHRAC seemed to be no benefit for stage II patients. Toxicities, such as hepatic toxicity and leucocyte decreasing, were mild and could be cured with medicine. Conclusions: Preoperative hepatic and regional arterial chemotherapy, in combination with surgical resection, could be able to reduce and delay the occurrence of liver metastasis and therefore improve survival rate in patients with stage III colorectal cancer. No significant financial relationships to disclose.

Association of interleukin-10 gene variation with breast cancer prognosis

Genetic polymorphisms are responsible for inter-individual variation and diversity and have been recently considered as the main genetic elements involved in the development and progression of cancer. We examined associations between common germline genetic variants in 7 genes involved in folate metabolism, cell proliferation and apoptosis, prostaglandin synthesis, detoxification of compounds and inflammation, and disease-free survival among women diagnosed with invasive breast cancer. DNA from up to 432 women was genotyped for 8 polymorphisms. The genotypes of each polymorphism were tested for association with disease-free survival using univariate and multivariate Cox regression analysis. The model was adjusted for known breast cancer prognostic factors. The rare allele of the IL-10 592C>A polymorphism was significantly associated with reduced disease-free survival (P = 0.018, risk ratio of recurrence (RR) = 1.45, 95% confidence interval (CI) = 1.06-1.98), which was not attenuated after adjusting for age at diagnosis, tumor size, lymph node status, clinical stage, histological grade, estrogen receptor status, progesterone receptor status, and treatment modalities (P = 0.019, RR = 1.48, 95% CI = 1.066-2.044). No association was found between MTHFR 677C>T, TGFB1 29T>C, FASLG 844C>T, FAS 1377G>A, FAS 670A>G, PTGS2 8473T>C and SULT1A1 638G>A polymorphisms and disease-free survival. Our data suggest that the rare allele of IL-10 592C>A may be a potential prognostic marker in breast cancer for disease-free survival.

Hypoplastic Left Heart Syndrome Links to Chromosomes 10q and 6q and Is Genetically Related to Bicuspid Aortic Valve

This study was designed to identify disease loci for hypoplastic left heart syndrome (HLHS) and evaluate the genetic relationship between HLHS and bicuspid aortic valve (BAV). Previously, we identified that HLHS and BAV exhibit complex inheritance, and both HLHS and BAV kindreds are enriched for BAV. However, the genetic basis of HLHS and its relationship to BAV remains unclear. Family-based nonparametric genome-wide linkage analysis was performed in kindreds ascertained by either an HLHS or BAV proband. Echocardiograms were performed on 1,013 participants using a sequential sampling strategy (33 HLHS kindreds, 102 BAV kindreds). The recurrence risk ratio of BAV in HLHS families (8.05) was nearly identical to that in BAV families (8.77). Linkage to chromosomal regions 10q22 and 6q23 with maximum logarithm of odds scores of 3.2 and 3.1, respectively, was identified in HLHS kindreds. In addition, 5 suggestive loci were identified (7q31, 11q22, 12q13, 14q23, and 20q11). We previously identified loci at chromosomes 18q22, 13q34, and 5q21 in BAV kindreds. The relationship between these loci was examined in the combined HLHS and BAV cohort and associations between loci were demonstrated (5q21, 13q34, and 14q23; 6q23 and 10q22; 7q31 and 20q11). Subsequent subsets linkage analysis showed a significant improvement in the logarithm of odds score at 14q23 only (4.1, p < 0.0001). These studies demonstrate linkage to multiple loci identifying HLHS as genetically heterogeneous. Subsets linkage analyses and recurrence risk ratios in a combined cohort provide evidence that some HLHS and BAV are genetically related.

Genome-Wide Linkage Analysis of TMPRSS2-ERG Fusion in Familial Prostate Cancer

Fusion of the 5'-untranslated region of androgen-regulated TMPRSS2 promoter with ETS transcription factor family members is found frequently in prostate cancers, and recent work suggests that the most common TMPRSS2-ERG fusion is associated with an aggressive clinical phenotype compared with fusion-negative prostate cancer. Thus far, analysis of the fusion has been limited to sporadic cases of prostate cancer. In the current study, we explore for an enrichment of TMPRSS2-ERG fusion in familial prostate cancer. TMPRSS2-ERG fusion was identified using a break-apart fluorescence in situ hybridization assay on tissue microarrays. Presence of TMPRSS2-ERG fusion was associated with higher Gleason scores (P = 0.027). Of 75 patients with established history of prostate cancer, we detected the TMPRSS2-ERG fusion in 44 (59%) patients. Almost three quarters (73%) of fusion-positive patients accumulated within 16 specific families whereas only 27% were single fusion-positive cases within one family. Based on reported prevalence rates, we calculated a sibling recurrence risk ratio of up to 18.9. A subset (63%) of families with uniformly TMPRSS2-ERG-positive prostate cancer underwent a genome-wide linkage scan at 500 markers. This revealed several loci located on chromosomes #9, #18, and X that were suggestive of linkage to the TMPRSS2-ERG fusion-positive prostate cancer phenotype with linkage-of-disease scores up to 2.16 and nonparametric linkage scores up to 2.77. This suggests the presence of an inherited susceptibility to developing the TMPRSS2-ERG fusion. Given the association of TMPRSS2-ERG fusion and aggressive prostate cancer, close surveillance of relatives of patients with established fusion-positive prostate cancer or a family history of prostate cancer in general would be warranted.

Long‐term outcomes and clinicopathologic differences of African‐American versus white patients treated with breast conservation therapy for early‐stage breast cancer

African-American (AA) and white patients with early-stage disease who were treated with breast conservation therapy (BCT) were examined to detect differences in clinicopathologic features and outcomes as a function of race. Clinical data from the charts of 2164 white and 207 AA patients treated with BCT, and p53 expression status on 444 patients (from an existing tissue database), were analyzed to detect differences between the 2 cohorts. The median follow-up was 7 years. There were no differences in the method of tumor detection, lymph nodes excised, surgical margin status, or chemotherapy/radiotherapy delivered, reflecting similar screening and treatment policies for AA women in the study community. Despite this, AA patient presented at a younger age, with higher T and N classifications, and more estrogen and progesterone negative and "triple negative" tumors (all P values < .016). Tumors in AA patients were p53 positive more often than tumors in white patients (P= .0003). At 10 years, AA patients had a higher rate of distant metastasis (20% vs 17%; P= .042), lymph node recurrence (6% vs 2%; P= .004), and breast recurrence (17% vs 13%; P= .036). There was no difference in overall survival between the 2 groups. On multivariate analysis, only lymph node recurrence (risk ratio of 3.140; 95% confidence interval, 1.396-7.063 [P= .0057]) remained significantly higher among AA women. In this cohort of uniformly treated patients, the authors found the expected clinicopathologic differences, but race was not found to be an independent predictor of local recurrence for AA patients when other confounding variables were taken into account in the multivariate model. These findings suggest that BCT is a reasonable option for appropriately selected AA patients. To the authors' knowledge, this is the largest study addressing outcomes after BCT for AA women published to date.

Genotype-Specific Recurrence Risks as Indicators of the Genetic Architecture of Complex Diseases

A statistic is introduced that relates discoveries made in genome-wide association (GWA) studies to patterns of disease risks among relatives. The genotype-specific recurrence risk (GSR) is the genotype-specific risk to relatives of known relationship to affected probands. The GSRs can be used for three purposes. (1) They can provide an independent test of whether an allele identified in a GWA study is associated with the disease. (2) They can provide a test of whether interactions among loci affecting the disease are multiplicative. (3) They can be used by genetic counselors to incorporate information from GWA studies for predicting the risk to relatives of known genotype. Under a multiplicative model of disease causation, the GSRs for a locus are the genotypic risks in probands for that locus multiplied by lambda(R)/lambda(jR), where lambda(R) is Risch's recurrence risk ratio and lambda(jR) is the contribution to lambda(R) from the locus of interest. If there is saturation of risk with increasing numbers of causative alleles, then observed GSRs for individuals with high-risk genotypes will be lower than predicted by the multiplicative model.

Stroke among Siblings in a Biethnic Community

Background: Mexican Americans (MAs) have an increased risk of stroke compared with non-Hispanic whites (NHWs), especially at younger ages. Little is known regarding patterns of familial aggregation of stroke and whether familial risk assessment might prove a potentially useful tool in assessing stroke risk in this population. This study’s objective was to estimate the sibling recurrence risk ratio (λ_s) for stroke and to compare this ratio between MAs and NHWs. Methods: Stroke and transient ischemic attack (TIA) cases (n = 181) between the ages of 45 and 64 years were identified by a population-based stroke study in a biethnic Texas community. λ_s was calculated overall and by ethnicity. Results: Siblings of ischemic stroke/TIA cases had a doubling in stroke risk compared to what would be expected based on national stroke prevalence estimates (λ_s = 1.92; 95% CI: 1.39–2.61). λ_s was 2.0 (95% CI: 1.39–2.81) among MA stroke/TIA cases and 1.66 (95% CI: 0.82–3.10) among NHW stroke/TIA cases. Conclusion: The sibling recurrence risk for stroke was elevated in MA stroke/TIA cases suggesting that further ischemic stroke genetic studies across ethnicities may be warranted. In addition, a positive family history could prove a useful factor in the clinical setting for identifying MAs at increased stroke risk.

Familial aggregation of psoriatic arthritis

Objectives:The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA.Methods:All available FDRs (full siblings,...

Familial Aggregation of Cryptorchidism--A Nationwide Cohort Study

Although cryptorchidism is the most common birth defect in boys affecting 4-9 percent of newborns and 1-2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977-2005. Using binomial log-linear regression, they estimated recurrence risk ratios (RRRs) of cryptorchidism for male twin pairs and first-, second-, and third-degree relatives of a cryptorchidism case. The RRR in same-sex twins was 10.1 (95% confidence interval (CI): 7.78, 13.1). The RRR among first-degree relatives was significantly higher among brothers (RRR = 3.52, 95% CI: 3.26, 3.79) than for offspring of a cryptorchidism case (RRR = 2.31, 95% CI: 2.09, 2.54). The RRR was also found to be significantly higher in maternal (RRR = 2.12, 95% CI: 1.74, 2.60) than paternal (RRR = 1.28, 95% CI: 1.01, 1.61) half brothers. In conclusion, inherited factors were found to have a moderate influence on the risk of cryptorchidism. The data are compatible with the hypothesis that maternal factors operating in utero are important for the risk of cryptorchidism.

Recurrence of spondylarthropathy among first-degree relatives of patients: a systematic cross-sectional study

Objective:To examine the recurrence of manifestations belonging to the spectrum of spondylarthropathy (SpA) in first-degree relatives of patients with SpA, and to estimate the recurrence risk ratio.Methods:Parents and siblings of...

DSM‐IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage

Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADHD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings.