Biomedical subjects

C E Aston

Publications and source records attributed to C E Aston.

At least 19 recordsLinked to original sources

PubMed2001

Effects of race, cigarette smoking, and use of contraceptive medications on resting energy expenditure in young women.

The prevalence of obesity is higher in Black women than in White women (JAMA 1994;272:205-11; Arch Pediatr Adolesc Med 1995;149:1085-91). Although it has been shown that Black women have a lower resting energy expenditure (REE), factors affecting REE remain unclear. This 1996-1997 study in Cincinnati, Ohio, assessed racial differences in REE and their determinants in a biracial cohort of 152 healthy young women aged 18-21 years. Two indirect calorimetric measurements were obtained during two overnight hospital admissions 10-14 days apart. Body composition was measured by using dual-energy x-ray absorptiometry. Mean REE (adjusted for body composition, smoking, and contraceptive medication use) was significantly (p = 0.04) lower by 71 kcal/day in Black women (1,453 (standard error, 21) kcal/day) than in White women (1,524 (standard error, 19) kcal/day). Smoking was associated with a REE that was 68 kcal/day higher for both groups (p = 0.03). A trend (p = 0.07) toward increased REE (by 46 kcal/day) was found with contraceptive medication use. In conclusion, young Black women had a significantly lower REE than did White women. Cigarette smoking significantly increased REE. The apparent presence of a more parsimonious energy metabolism in Black women suggests that maintenance of energy homeostasis requires particular vigilance in this high-risk population.

Adolescent↗

PubMed2001

Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus.

Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology, but, to date, efforts using genetic linkage to find the susceptibility genes for either phenotype have met with limited success. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically homogeneous at loci important to both SLE and vitiligo and, hence, have increased power for detection of linkage. We therefore evaluated genomewide microsatellite-marker-scan data for markers at an average marker density of approximately 11 cM in these 16 European-American pedigrees and identified a significant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effects.

Chromosome Mapping↗

PubMed2001

Single nucleotide polymorphism in prohibitin 3' untranslated region and breast-cancer susceptibility.

The RNA encoded by the 3' untranslated region of the prohibitin gene arrests cell proliferation by blocking the transition between the G1 and S phases of the cell cycle. The product of a variant allele (T allele) is inactive. We did a case-control study of prohibitin genotype in 205 women with breast cancer and 1046 healthy controls. The results showed an association between the T allele and breast cancer in women who reported a first-degree relative with the disease (odds ratio 2.5, p=0.005). An even stronger association was found in a subset of women diagnosed at or before age 50 years (4.8, p=0.003). These data suggest that prohibitin genotyping has value in assessing risk of breast cancer in women aged 50 years or younger with at least one first-degree relative with the disease.

Adult↗

PubMed2001

Candidate gene analysis in premature pubarche and adolescent hyperandrogenism.

OBJECTIVE: To identify genetic markers associated with premature pubarche in children and hyperandrogenism in adolescent girls. DESIGN: Association study. SETTING: Academic research environment. PATIENT(S): Forty children with premature pubarche (PP), 29 adolescent girls with hyperandrogenism (HA), and 15 healthy control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genetic variations at five loci selected because of known associations with hyperandrogenism, insulin resistance, hyperinsulinemia, or obesity. RESULT(S): Heterozygosity for CYP21 mutations was identified in 14 of 40 (35%) PP, 8 of 29 (28%) HA, and 1 of 30 (3%) controls. Heterozygosity for HSD3B2 variants was identified in 3 of 40 (7.5%) PP, 5 of 29 (17%) HA, and 0/15 controls. Among the PP, 11 of 80 (14%), 5 of 80 (6%), and 7 of 80 (9%) alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the HA, 5 of 58 (8.6%), 3 of 58 (5%), and 6 of 58 (10%) alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the control participants, variant allele frequency was 1 of 30 (3.3%) for IRS-1, 2 of 30 (6.6%) for GRL, and 2 of 30 (6.6%) for ADRB3. CONCLUSION(S): Our findings suggest that the development of PP and HA can be associated with the occurrence of multiple sequence variants at five susceptibility loci, especially steroidogenic enzyme genes. This approach offers a novel paradigm to investigate and identify the genetic factors relevant to polycystic ovary syndrome.

3-Hydroxysteroid Dehydrogenases↗

PubMed2001

Inconsistent effects of the proline12 --> alanine variant of the peroxisome proliferator-activated receptor-gamma2 gene on body mass index in children and adolescent girls.

OBJECTIVE: To ascertain whether variation in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription factor affecting both adipocyte differentiation and insulin sensitivity, influences body mass index (BMI). DESIGN: Association study. SETTING: Academic research environment. PATIENT(S): Children with premature pubic hair and adolescent girls with hyperandrogenism. INTERVENTION(S): Assay for P12A and P115Q variants and measure BMI. MAIN OUTCOME MEASURE(S): BMI and PPAR-gamma genotypes. RESULT(S): Fourteen subjects were heterozygous for P12A; two were homozygous. None carried the P115Q allele. No significant differences in BMI or basal androstenedione concentrations between P12 carriers and noncarriers were found. Thirty-nine subjects had BMI values at two time points; mean BMI was significantly greater in the P12A carriers at time point 2. Those P12A carriers obese at time point 1 became more obese; lean mutation carriers tended to remain lean. Annual rate of increase in BMI was significantly greater in the P12A carriers than the noncarriers. CONCLUSION(S): Our findings suggest that P12A may be a genetic marker indicating risk for obesity persisting into adolescence. Future studies are needed to determine whether the divergent effects of P12A persist into adulthood, to elucidate the mechanism of this effect, and to replicate our findings in other populations.

Amino Acid Sequence↗

PubMed2001

Motivations and concerns of patients with access to genetic testing for hereditary pancreatitis.

OBJECTIVES: Direct DNA testing is now available for hereditary pancreatitis (HP). This study aimed to identify the factors that motivated individuals to participate in research and to determine how research participants used their genetic test results. METHODS: A survey was mailed to 247 participants (110 male, 137 female) who were > or =18 yr of age and living in the US. Data analysis was primarily a description of frequency distribution of the responses. RESULTS: Ninety-one of 247 participants (37%) completed the survey. Of the 55 female and 36 male respondents, 60% were 31-55 yr old, and a total of 54% tested positive for HP. The most common reason for participating in research was "to help a relative/family member" (61%), and genetic testing was pursued because of "the disturbance of seeing affected relatives" (48%) and "the desire to help future generations" (33%). Perceived risk of developing HP in the future was the least important motivating factor in seeking genetic testing. Sixty-two percent of respondents had received their genetic test results. All but one chose to share their results with at least one person: most often with family members (96%) and physicians (62%), and least often with insurance companies (4%). The most common influential factor in withholding information was "the fear of insurance discrimination" (23%). CONCLUSIONS: The major motivations to participate in the HP genetic research study were to obtain genetic testing and to help current family members and future generations. The major concern was insurance discrimination. Participants clearly appreciate the availability of genetic testing for HP. These results suggest that a mechanism to disclose results to research participants should be considered, and effective ways to protect at-risk individuals from insurance discrimination must remain a genetics health care priority.

Adult↗

PubMed2001

Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins.

BACKGROUND: Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. AIM: Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. METHODS: Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. RESULTS: Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS: Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition.

Adolescent↗

PubMed2001

Genetic effect of two APOA repeat polymorphisms (kringle 4 and pentanucleotide repeats) on plasma Lp(a) levels in American Samoans.

Elevated plasma lipoprotein(a) [Lp(a)] level has been established as an independent risk factor for atherosclerosis and coronary heart disease. Considerable ethnic group differences in the distribution of plasma Lp(a) levels have raised public health concerns. Recently, we have reported that Samoans have the lowest plasma Lp(a) levels of any population group. In the present investigation, we report the contribution of two apolipoprotein(a) (APOA) polymorphisms, the kringle 4 type 2 (K4) repeat and the pentanucleotide repeat (PNR), in affecting plasma Lp(a) levels in an American Samoan sample (n = 309). The K4 repeats ranged in size from 15 to 40. The common alleles contained repeats ranging from 26 to 36 with allele frequencies between 5.5% to 9.7%, and these accounted for 82% of all alleles. An inverse relationship between K4 repeat number and plasma Lp(a) level was observed for single-banded (r = -0.59, p = 0.0001) and double-banded phenotypes (r = -0.50, p = 0.0001). This polymorphism explained 60% of the variation in plasma Lp(a) level in American Samoans. For the PNR polymorphism, five different repeat alleles and eight different genotypes were identified; the most common allele was eight repeats. The *8 PNR allele was associated with a wide range of K4 repeats, the *9 PNR allele with larger K4 repeats (25-40), and the *10 PNR with smaller K4 repeats (15-24). Analysis of variance (ANOVA) revealed that the PNR polymorphism accounts for 2.1% of the variability in plasma Lp(a) levels in this sample, when the K4 repeat polymorphism was taken into account. Our data show that common polymorphisms in the APOA gene are major determinants of plasma Lp(a) variation in American Samoans.

Adult↗

PubMed2000

Racial and genetic determinants of plasma factor XIII activity.

Factor XIII (F XIII), a plasma transglutaminase, is essential for normal hemostasis and fibrinolysis. Plasma F XIII consists of two catalytic A (F XIIIA) and two non-catalytic B (F XIIIB) subunits. Activated F XIII is involved in the formation of fibrin gel by covalently crosslinking fibrin monomers. As the characteristics of the fibrin gel structure have been shown to be associated with the risk of coronary heart disease (CHD), F XIII activity may play a seminal role in its etiology. In this investigation, we determined plasma F XIII activity in two racial groups, including Asian Indians (n = 258) and Chinese (n = 385). Adjusted plasma F XIII activity was significantly higher in Indian men (142 vs. 110%; P<0.0001) and women (158 vs. 111%; P<0.0001) than their Chinese counterparts. As compared to Indians where the distribution of F XIII activity was almost normal, in Chinese it was skewed towards low activity. In both racial groups, bivariate and multivariate analyses showed strong correlation of F XIII activity with plasma fibrinogen and plasminogen levels. Race explained about 25% of the variation in F XIII activity even after the adjustment of significant correlates. We also determined the contribution of common genetic polymorphisms in the F XIIIA and F XIIIB genes in affecting plasma F XIII activity. Both loci showed significant and independent effects on plasma F XIII activity in Indians (F XIIIA, P< 0.01; F XIIIB, P<0.05) and Chinese (F XIIIA, P<0.0001; F XIIIB, P<0.13) in a gene dosage fashion. This study shows that both racial and genetic components play a significant role in determining plasma F XIII activity, and consequently it may affect the quantitative risk of CHD.

Adult↗

PubMed2000

Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels.

The lipoprotein lipase (LPL) enzyme plays a major role in lipid metabolism, primarily by regulating the catabolism of triglyceride (TG)-rich lipoprotein particles. The gene for LPL is an important candidate for affecting the risk of atherlosclerosis in the general population. Previously, we have shown that the HindIII polymorphism in intron 8 of the LPL gene is associated with plasma TG and HDL-cholesterol variation in Hispanics and non-Hispanic whites (NHWs). However, this polymorphism is located in an intron and hence may be in linkage disequilibrium with a functional mutation in the coding region or intron-exon junctions of the LPL gene. The aim of this study was to initially screen the LPL coding region and the intron-exon junctions by single-strand conformation polymorphism (SSCP) analysis for mutation detection in a group of 86 individuals expressing the phenotype of high TG/low HDL, followed by association studies in a population-based sample of 1,014 Hispanics and NHWs. Four sequence variations were identified by SSCP and DNA sequencing in the coding region of the gene, including two missense mutations (D9N in exon 2 and N291S in exon 6), one samesense mutation (V108V in exon 3), and one nonsense mutation (S447X in exon 9). Multiple regression analyses, including these four mutations and the HindIII polymorphic site, indicate that the association of the HindIII site with plasma TG (P=0.001 in NHWs and P=0.002 in Hispanics) and HDL-cholesterol (P=0.007 in NHWs and P=0.127 in Hispanics) is independent of all other LPL variable sites examined. These observations reinforce the concept that the intronic 8 HindIII site is functional by itself and provide a strong rationale for future comprehensive functional studies to delineate its biological significance.

Adult↗

PubMed2000

DNA sequence variation in human apolipoprotein C4 gene and its effect on plasma lipid profile.

Human apolipoprotein C-IV (apoC-IV, protein; APOC4, gene) is a new member of the APO E/C1/C2 gene cluster. In transgenic mice, human apoC-IV is predominantly associated with very low-density lipoprotein (VLDL) and thus may play an important role in lipid metabolism. To our knowledge, the extent and nature of APOC4 genetic variation and its role in lipid metabolism are unknown. In this study we have assessed the presence of genetic variation in all three exons of APOC4 and their flanking intronic sequence by SSCP and DNA sequencing. A total of five point mutations were observed, including two in the non-coding part of exon 1 (A609G and G620A), two in exon 2 (codons 36 and 52) and one in exon 3 (codon 96). The three mutations in exons 2 and 3 predict amino acid substitutions, Leu36Pro, Gly52Asp, and Leu96Arg. The frequencies of the variant alleles were: 0.010 for 609G, 0.039 for 620A, 0.502 for Pro36, 0.003 for Asp52 and 0.357 for Arg96. Significant pairwise linkage disequilibrium was observed between five of the ten APOC4 pairs, including nt. 620/codon 36, nt. 620/codon 96, codon 36/codon 52, codon 36/codon 96 and codon 52/codon 96. A general linear model analysis reveled a significant association of the Leu36Pro and the Leu96Arg polymorphisms with triglyceride levels in women. This is consistent with the proposed role of apoC-IV in triglyceride metabolism. The characterization of APOC4 genetic variation may lead to the identification of a specific role of apoC-IV in lipid metabolism or in other physiologic pathways.

Adult↗

PubMed2000

Inheritance of pancreatic cancer in pancreatic cancer-prone families.

Families are being increasingly recognized as carrying an inherited susceptibility for pancreatic cancer, apparently unrelated to any currently recognized syndrome. The authors provide a review of the current evidence for familial susceptibility to pancreatic cancer. A formal segregation analysis of the pattern of inheritance of pancreatic cancer in 70 families from the National Registry for Familial Pancreatic Cancer is described. This analysis suggests a single major gene with an autosomal dominant mode of inheritance controlling susceptibility for pancreatic cancer in these families.

Adenocarcinoma↗

PubMed2000

Plasma lipoprotein(a) distribution and its correlates among Samoans.

Plasma lipoprotein(a) [Lp(a)]-consisting of a disulfide-linked complex of apolipoprotein B and apolipoprotein (a)--levels are considered to be an independent risk factor for coronary heart disease. There are considerable ethnic group differences in the distribution of plasma Lp(a) levels that raise public health concerns. Although plasma Lp(a) distribution has been determined in various ethnic groups, no such information is available in Pacific Islanders. In this study we have determined the distribution and correlates of plasma Lp(a) in population-based samples of 361 American Samoans (145 men, 216 women) and 560 Western Samoans (265 men, 295 women), aged 20-70 years. Plasma Lp(a) levels were measured using a commercial enzyme-linked immunosorbent assay. The distribution of plasma Lp(a) levels in both groups was highly skewed with 73% and 65% of values in the 0-5 mg/dl range in American Samoans and Western Samoans, respectively. The mean (6.4 mg/dl) and median (2.2 mg/dl) Lp(a) levels in pooled Samoans were significantly lower when compared with other ethnic groups using the same measurement kit. Plasma Lp(a) correlated significantly with total and LDL cholesterol in both genders after correcting for the contribution of Lp(a) cholesterol, and with apolipoprotein B in women after the correction for Lp(a)-apoB, but not with age, smoking, alcohol intake, or body mass index. Our data show that Samoans, Polynesians of Pacific Islands, have strikingly lower Lp(a) levels than all other reported population groups. These data are consistent with the hypothesis that genetic factors account for interethnic group variation in plasma Lp(a) levels.

Adult↗

PubMed2000

The role of heterozygosity for CYP21 in the polycystic ovary syndrome.

The phenotypic heterogeneity recognized in congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency appears to extend to 21hydroxylase (CYP21) mutation carriers. To begin the search for modifying loci responsible for this phenotypic heterogeneity, we performed CYP21 genotype analysis and assays for three candidate modifier loci on genomic DNA samples obtained from 30 adolescent girls with hyperandrogenism, 14 healthy control women, and 15 female obligate CYP21 mutation carriers. The frequency of heterozygosity for CYP21 mutations was increased in women with symptomatic hyperandrogenism (10/30) compared to healthy controls (1/14). There were no significant differences in the frequencies of the modifier variants among the three groups. Although the small sample size precludes strong conclusions, CYP21 nonsense mutation carriers tend to be asymptomatic while missense mutation carriers, i.e. V281L, appear to manifest a PCOS phenotype. Evaluation of additional modifying loci in larger series of patients will help identify new genetic markers associated with PCOS.

Adolescent↗

PubMed1999

A novel mutation in the apolipoprotein E gene (APOE*4 Pittsburgh) is associated with the risk of late-onset Alzheimer's disease.

Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing techniques, we identified a unique missense mutation (T-->C) in exon 3 of the APOE gene which resulted in the substitution of pro-28 for leu-28. We screened 1118 White cases of late-onset (>60 years) Alzheimer's disease (AD) from three independent centers (Pittsburgh = 489, Indiana = 319, Mayo Clinic Rochester = 310) and 1123 controls (607 clinically assessed and 516 individuals randomly ascertained from the general population). Two of the 1123 control subjects had the pro-28 mutation (0.18%). However, this mutation was observed in heterozygous state in 2.66, 2.51 and 1.94% of the AD cases from Pittsburgh, Indiana and Mayo Clinic Rochester, respectively, with an overall frequency of 2.42%. All individuals with this mutation were carriers of the APOE*4 allele and hence the mutation was denoted as APOE*4 Pittsburgh (APOE*4P). Compared with the non-E*4P carriers, the E*4P carriers were associated with an increased risk of AD (odds ratio (OR) 13.2) and this risk remained significant even after adjusting for the known effect of APOE*4 (OR 5.4). The risk associated with the E*4P/E*4 combination was about five times (OR 29.1) the risk attributed to APOE*4 carriers alone (OR 5.7). Our data indicates that the new mutation most likely exists in cis-orientation with APOE*4 and is associated with increased risk of developing AD.

Adult↗

PubMed1999

Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks.

Genetic studies carried out mainly in European and European-derived populations have shown that common polymorphisms in genes coding for apolipoproteins are significant determinants of serum lipoprotein-lipid levels variation. However, except for a few sporadic studies, the distribution of apolipoprotein polymorphisms and their association with serum lipoprotein-lipid levels have not been evaluated systematically in African or African-derived populations. In this investigation we have studied five apolipoprotein polymorphisms, including APOA1/MspI-75 bp, APOA1/MspI+83 bp, APOC3/PvuII, APOE, and APOH in 786 Africans (493 men, 293 women) from Nigeria. The sample is comprised of Nigerian civil servants consisting of 462 junior staff (less affluent) and 324 senior staff (more affluent) where staff status is a correlate of their socioeconomic status. We first examined genetic associations in the total sample stratified by gender to determine the role of apolipoprotein polymorphisms in affecting serum lipid profile in the general population, and then by staff status to evaluate possible gene-environment interactions. In the total sample, the APOC3/PvuII polymorphism showed significant effect on HDL-cholesterol (P = 0.029) and HDL3-cholesterol (P = 0.009) in women, and the APOE polymorphism was significantly associated with total cholesterol (P = 0.031) and LDL-cholesterol (P = 0.0006) in women. Multiple regression analyses showed that the APOC3/PvuII polymorphism accounts for about 2 and 3% of the variation in HDL-cholesterol and HDL3-cholesterol, respectively, in women; while the APOE polymorphism accounted for about 5 and 6% of the variation in total- and LDL-cholesterol, respectively, in women. Whereas the association of the APOE polymorphism was independent of the staff status, the significant affect of the APOC3/PvuII polymorphism on HDL- and HDL3-cholesterol was confined to senior staff women where it explained about 7% of their variation. We also observed an interaction between staff and the APOH polymorphism in affecting cholesterol levels. The APOH polymorphism showed significant association with total cholesterol (P = 0.010) and LDL-cholesterol (P = 0.016) in senior staff women and explained about 7 and 5% of their phenotypic variations, respectively. These data indicate that gene-environment interaction may play an important role in affecting serum lipid profile in African populations.

Adult↗

PubMed1999

Lung cancer risk in families of nonsmoking probands: heterogeneity by age at diagnosis.

In an earlier investigation, we did not detect a major genetic component to lung cancer in families of nonsmoking lung cancer probands. However, heterogeneity with respect to familial aggregation, based on probands' age at diagnosis, was evident. We reanalyzed our previously collected data of 257 families, stratified by age at diagnosis of the probands, using complex segregation analysis. We specifically tested the effects of a Mendelian diallelic gene, history of tobacco use, and history of selected chronic lung diseases in families with a proband diagnosed at the age of 60 years or older and in families with a younger proband (i.e. , under 60 years of age). Cases were identified from the Metropolitan Detroit Cancer Surveillance System. Information on lung cancer occurrence, smoking history, and chronic respiratory diseases in first-degree relatives was obtained for 210 older probands and for 47 younger probands. In older probands' families, no evidence of a major genetic effect was detected. A history of emphysema and tobacco-smoke exposure were found to be significant risk factors. In younger probands' families, a Mendelian codominant model with significant modifying effects of smoking and chronic bronchitis best explained the observed data. Our results suggest the presence of a high-risk gene contributing to early-onset lung cancer in a population where the probands are nonsmokers.

Adult↗

PubMed1999

A simple allele sharing statistic for multiple locus systems.

For complex disorders where the actions of several interacting loci must be taken into account, current methods of joint linkage analysis are problematic. We have undertaken an exploration of simultaneous search statistics originally proposed by Dupuis et al. [1995]. Additionally, we have extended these methods slightly and propose here a simple simultaneous search statistic based upon the single-point allele sharing statistic calculated from GENEHUNTER (GH). The use of conditional search techniques is also explored.

Alleles↗