Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Etiological heterogeneity in Hodgkin's disease: HLA linked and unlinked determinants of susceptibility independent of histological concordance

Forty-one multiplex families, from published sources and new data from the National Cancer Institute, segregating for Hodgkin's disease and HLA, have been studied. A reanalysis of these data strongly suggests a recessive mode of inheritance for susceptibility to Hodgkin's disease. The HLA haplotype sharing data between affected relatives demonstrate that approximately 60% of cases in multiplex families are due to an HLA-linked susceptibility gene, the remaining 40% being due to other familial factors. The data clearly support the hypothesis of etiological heterogeneity for Hodgkin's disease, with both HLA-linked and HLA-unlinked factors being responsible. Finally, there is an increased concordance of histological types between affected relatives, but this concordance seems independent of HLA sharing.     

Optimal Selection of Sib Pairs from Random Samples for Linkage Analysis of a QTL Using the EDAC Test

Percentages of extremely concordant and extremely discordant sib pairs are calculated that maximize the power to detect a quantitative trait locus (QTL) under a variety of circumstances using the EDAC test. We assume a large fixed number of randomly sampled sib pairs, such as one would hope to find in the large twin registries, and limited resources to genotype a certain number of selected sib pairs. Our aim is to investigate whether optimal selection can be achieved when prior knowledge concerning the QTL gene action, QTL allele frequency, QTL effect size, and background (residual) sib correlation is limited or absent. To this end we calculate the best selection percentages for a large number of models, which differ in QTL gene action allele frequency, background correlation, and QTL effect size. By averaging these percentages over gene action, over allele frequency, over gene action, and over allele frequencies, we arrive at general recommendations concerning selection percentages. The soundness of these recommendations is subsequently in a number of test cases.     

Path analysis and sib-pair linkage

When the distance between linked loci is expressed in terms of the correlation between the identity-by-descent (idb) values of the loci, then a path model may be used to order loci with data on sib-pairs and their parents. The relationship between the recombination fraction and the correlation coefficient is developed and a method for fitting a covariance matrix predicted by a specific ordering of loci to an observed covariance matrix is proposed. © 1993 Wiley-Liss. Inc.     

Validation of Probabilistic Linkage to Match De-identified Ambulance Records to a State Trauma Registry

Objectives: To validate the accuracy of using probabilistic linkage for matching de‐identified ambulance records to a state trauma registry. Methods: This was a retrospective cohort analysis. Three thousand nine hundred nineteen true matches between ambulance and state trauma registry data from 1998 to 2003 were identified by deterministic matching on trauma identification number and verified by human review. Two thousand thirty‐eight ambulance records from trauma patients not meeting criteria for a true match, and an identical number of trauma registry records randomly selected from the one local county served by a different EMS provider, were included as nonmatches. There were 17 variables considered for linkage, which included the following: age, gender, race, county, hospital, date, rural setting, call and arrival times, mechanism, penetrating injury, vital signs, intubation, and intoxication. Probabilistic linkage was used to link the two data sets, using seven different combinations of common variables (maximum, 17; minimum, 4). The sensitivity and specificity of identifying true matches and nonmatches (95% confidence intervals [95% CI]) were calculated for each combination of variables. Results: Using all 17 available variables, 3,766 of 3,919 true matches were appropriately linked (sensitivity, 96.1%; 95% CI = 95.4% to 96.7%), with eight mismatches (specificity, 99.6%; 95% CI = 99.2% to 99.8%). Sensitivity fell below 95% with < 15 variables; however, sensitivity was very dependent on the inclusion of variables with high discriminatory power. Specificity remained >98% regardless of the number of variables included. Conclusions: Probabilistic linkage is a valid method for matching ambulance records to a trauma registry without the use of patient identifiers; however, the sensitivity of identifying true matches is critically dependent on the number and type of common variables included in the analysis.     

中国人D13S301位点的微卫星多态及其应用价值

率先在国内应用ＰＣＲ技术扩增Ｗｉｌｓｏｎ病（ＷＤ）基因内部Ｄ１３Ｓ３０１位点的微卫星多态，通过变性聚丙烯酰胺凝胶电泳检测扩增产物，对８０名正常中国人进行了检测，结果具有１２种不同长度的等位片段，多态信息含量（ＰＩＣ值）为０．８８３，表明该位点在中国人群中具有长度多态性及较高的应用价值。应用该位点对１０个ＷＤ家系进行连锁分析，在２４名无症状个体中检出１２名基因携带者，７名正常纯合子及２名症状前患者，进一步证实该位点可用于ＷＤ的症状前诊断及杂合子筛选。     

Monoamine oxidases and alcoholism. II. Studies in alcoholic families

Thirty-five alcoholic families have been studied to investigate the relationship between DNA markers at the monoamine oxidase (MAO) loci and (1) platelet activity levels and (2) alcoholism. A quantitative linkage analysis failed to reveal any evidence that the variation in activity levels cosegregates with the DNA markers. A sib-pair analysis did not reveal a significant excess of MAO haplotype sharing among alcoholic sibs, although the deviation from random sharing was in the direction consistent with an X-linked component. A reanalysis of platelet MAO activity levels in a subset of these families revealed that the lower levels previously found in alcoholics is more likely due to the differences between males and females. Only among males and only when a “broad” definition of alcoholism is used (and MAO activity levels are transformed to normality) does it appear that alcoholics have depressed activities compared to nonalcoholics. Finally, when the confounding due to gender difference is removed, no differences between type I and type II alcoholics are found in these families. © 1995 Wiley-Liss, Inc.     

Obesity in youth and middle age and risk of colorectal cancer in men

To investigate an association between colon cancer and obesity during early adulthood—a potentially important period in the etiology of this disease—the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942–43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972–86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI]=1.4–3.2) and 1.7 (CI=1.1–2.5), at ages 15–29 and in prediagnostic years, respectively. These associations were additive and idependent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI=1.8–4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.The authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii. Address correspondence to Dr Le Marchand, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA. This work was supported in part by Public Health Service grant 5-R29-CA44503 and contract NO1-CN-55424 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.     

Labman and Linkman: A data management system specifically designed for genome searches of complex diseases

Two programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker-allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user-specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports. The programs include features critical for conducting genome searches of complex diseases: They are easy-to-use, well-tested, and reliable. Data from multi-center investigations can be easily combined for analysis. Moreover, they include extensive error-checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS. © 1994 Wiley-Liss, Inc.