Genetic influences in irritable bowel syndrome: a twin study

BACKGROUND: Aggregation of symptoms of abdominal pain or bowel disturbance has been described in the families of patients with irritable bowel syndrome (IBS). This may be due to environmental factors, including learned responses to abdominal symptoms or a genetic contribution to the etiology of IBS. OBJECTIVES: To determine the relative contribution of genetic factors to IBS by evaluating IBS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 4,480 unselected twin pairs identified from a national volunteer twin register were asked to complete a validated questionnaire. IBS was defined by the Rome II criteria. RESULTS: A total of 5,032 subjects replied (56% response rate). One thousand eight hundred seventy complete twin pairs were evaluable; 888 MZ pairs (82 male pairs, mean age 51, SD 13 (range 19-81) yr) and 982 DZ pairs (69 male pairs, age 52, SD 13 (20-82) yr). The prevalence of IBS was 17% in MZ and 16% in DZ twins. There was no significant difference in casewise concordance rates between the MZ and DZ twins (28%vs 27%, p=NS). Logistic regression analysis revealed that decreasing age and increasing psychosomatic score were independently associated with IBS. Multifactorial liability threshold modeling suggested that a combination of unique and shared environmental factors provided the best model for IBS. In contrast, somatization was shown to be moderately heritable. CONCLUSION: Genetic factors are of little or no influence on IBS where the predominant influences appear to be environmental.     

The relative importance of genetic and environmental factors in the aetiology of thyroid nodularity: a study of healthy Danish twins

BACKGROUND: A large proportion of healthy, euthyroid, nongoitrous individuals have thyroid nodules. The aetiology of these ultrasonographically detected morphological abnormalities is largely unknown. Factors such as age, gender, iodine intake, smoking and parity are associated with nodularity of the thyroid. Whether there is a genetic susceptibility is unclear. AIM: To gain insight into the aetiology of thyroid nodularity by investigating a large cohort of healthy euthyroid monozygotic and dizygotic twins. DESIGN: A cross-sectional twin study. PARTICIPANTS: A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ) and 49 opposite sex (OS) twin pairs were investigated. MEASUREMENTS: Probandwise concordance and tetrachoric correlations. Quantitative genetic modelling was used to elucidate the relative importance of genetic and environmental effects for the variation in the liability of nodularity. RESULTS: A higher concordance rate for thyroid nodularity was found in MZ twins [0.57 (95% CI 0.36-0.76)] than in DZ twins [0.36 (95% CI 0.17-0.56, P = 0.074)]. The same was true for tetrachoric correlations: 0.67 (95% CI 0.34-0.87) in MZ twins and 0.17 (CI - 0.28-0.56, P = 0.053) in DZ twins. The difference, although not significant, was more pronounced for multiple nodules than for solitary nodules. Controlling for covariates (age, gender and smoking habits), it was calculated that genetic factors accounted for 67% (95% CI 35-87%) and environmental factors for 33% (95% CI 13-65%) of the individual differences in the liability to thyroid nodularity. CONCLUSIONS: This study suggests that genetic factors are of aetiological importance for thyroid nodularity in clinically healthy and euthyroid individuals, and indicates a difference in the aetiology of solitary and multiple thyroid nodules.     

Widespread pain among 11-year-old Finnish twin pairs

OBJECTIVE: To examine the prevalence of widespread musculoskeletal pain (WSP) symptoms in 11-year-old Finnish twins and to determine the relative role of genetic and environmental factors in the etiology of WSP. METHODS: Data on current pain items were collected from 1995 to 1998 from a national sample of Finnish families with 11-year-old twins born between 1984 and 1987. The presence of WSP was determined using a validated questionnaire method. Pairwise similarity was computed for 583 monozygotic (MZ) pairs, 588 same-sex dizygotic (DZ) pairs, and 618 opposite-sex DZ twin pairs. Variance components for genetic and environmental factors were estimated using biometric structural equation modeling techniques. RESULTS: The prevalence of WSP was 9.9%, with no sex difference. The majority of twin pairs with WSP were discordant. The tetrachoric correlations for male MZ (r = 0.38), male DZ (r = 0.37), female MZ (r = 0.59), female DZ (r = 0.54), and opposite-sex pairs (r = 0.43) showed little difference by zygosity. Female pairs were more concordant than male pairs among both MZ and DZ twins. Biometric model-fitting indicated that genetic factors did not account for the pattern of twin similarity. Among boys 35%, and among girls 56%, of the variation in liability to WSP could be attributed to shared familial environmental effects. The remainder was attributed to unshared environmental effects. CONCLUSION: Genetic factors seem to play at most a minor role in WSP in 11-year-old twins, and environmental factors shared by family members account for a substantial proportion of the variability in WSP.     

Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection?

BACKGROUND: Genetic factors play a role or roles in the etiology of peptic ulcer disease and the acquisition of Helicobacter pylori infection. OBJECTIVE: To evaluate the relative importance of genetic and environmental influences as well as the importance of H. pylori on peptic ulcer disease. DESIGN: Cross-sectional study on monozygotic (MZ) and dizygotic (DZ) twins, reared apart or together. PARTICIPANTS: Twins of the subregistry of the Swedish Twin Registry included in the Swedish Adoption/Twin Study of Aging. MEASUREMENTS: Peptic ulcer disease and H. pylori status were assessed in MZ and DZ twin pairs reared apart or together. A total of 258 twin pairs had information regarding H. pylori status and history of peptic ulcer. Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG. RESULTS: The intraclass correlations for peptic ulcer disease for MZ twins reared apart and together and DZ twins reared apart and together were 0.67, 0.65, 0.22, and 0.35, respectively, which indicates that genetic effects are important for liability to peptic ulcer. The correlation coefficient for MZ twins reared apart (0.67) provides the best single estimate of the relative importance of genetic effects (heritability) for variation in liability to peptic ulcer disease, and structural model fitting analyses confirmed this result (heritability, 62%). The cross-twin cross-trait correlations for MZ and DZ twins were examined to determine whether genetic effects for peptic ulcer were shared with or independent of genetic influences for H. pylori. The cross-correlations for MZ and DZ twins were almost identical (0.25 and 0.29, respectively), suggesting that familial environmental rather than genetic influences mediate the association between peptic ulcer disease and H. pylori infection. CONCLUSIONS: Genetic influences are of moderate importance for liability to peptic ulcer disease. Genetic influences for peptic ulcer are independent of genetic influences important for acquiring H. pylori infection.     

The genetic contribution to carpal tunnel syndrome in women: a twin study

OBJECTIVE: To assess the relative genetic and environmental contribution to carpal tunnel syndrome (CTS) using a classic twin study of monozygotic (MZ) and dizygotic (DZ) twins.METHODS:The study group comprised unselected female twin pairs, between 20 and 80 years of age, from the St Thomas' UK Adult Twin Registry. Individuals completed a questionnaire that included details on potential risk factors for CTS. The diagnosis of CTS was made using a standardized hand pain diagram and validated criteria. The genetic contribution to CTS was assessed using variance component and regression methods, the heritability was adjusted for environmental confounders. The role of individual risk factors was assessed by a nested case-control study.RESULTS: An overall prevalence of 14.2% for CTS was found in a population of 4,488 females, comprising 867 MZ and 970 DZ twin pairs, and 814 singletons. The concordance for CTS was significantly higher in MZ compared with DZ twins (case-wise concordance values of 0.35 and 0.24 respectively, with a significantly increased MZ:DZ ratio of 1.48; P = 0.03). Modeling produced a heritability estimate of 0.46 (95% CI 0.34-0.58) that was essentially unchanged after adjustment for environmental risk factors including age, body mass index, physical activities, and hormonal/reproductive factors. No major influence of any individual risk factor was seen in the case-control analysis of 520 cases and 3,154 controls, apart from a modest association with menopausal status with an increased risk of 1.53 and 1.43 in the peri and postmenopausal groups. There was no overall effect of age or body mass index.CONCLUSION: This is the first study to explore the genetic component of CTS. Our data show that up to half of the liability to CTS in women is genetically determined, and this appears to be the single strongest risk factor, with only minor contributions from known environmental factors. Further studies should focus on genetic mechanisms that may lead to tests for susceptibility and detection of those at risk of developing CTS.     

The genetic contribution to radiographic hip osteoarthritis in women: results of a classic twin study

OBJECTIVE: To assess the genetic contribution to radiographic hip osteoarthritis (OA) by measuring the distribution of disease features in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A population-based, cross-sectional study was conducted of 135 MZ and 277 DZ healthy female twin pairs, 50 years of age and older, who were recruited into the St. Thomas' UK Adult Twin Registry. Pelvic radiographs were read by a single observer who was blinded to the pairing and zygosity of the twins. The films were assessed for overall OA grade using a modification of the Kellgren and Lawrence scheme, and assessed for individual radiographic features. RESULTS: There was evidence of significant familial clustering for grade I and grade II OA changes, with an excess concordance in MZ twins compared with DZ twins, suggesting a genetic effect. The MZ versus DZ excess was also apparent for those classified as having more severe disease, although the number of pairs with these disease features was small. Familial clustering attributable to genetic factors was evident for joint space narrowing of <2.5 mm. Familial, but not genetic, clustering was seen for subchondral sclerosis. The number of pairs concordant for definite osteophytes in the sample was too low to assess this feature alone. These results translate into a significant heritability of 58% for OA overall and 64% for joint space narrowing. The heritability estimates decreased a little when the potential confounding influences of age, body mass index, and hip bone density were taken into account. CONCLUSION: Genetic factors have a significant contribution to OA at the hip in women and account for approximately 60% of the variation in population liability to the disease.     

The genetic epidemiology of joint hypermobility: a population study of female twins

OBJECTIVE: To estimate the genetic influence on joint hypermobility in an unselected population using a classic twin study design. METHODS: A self-report questionnaire on joint hypermobility as well as data on age, height, weight, estrogen replacement therapy, and menopause status were obtained from 483 monozygotic (MZ) and 472 dizygotic (DZ) unselected female twin pairs ages 21-81 years who were registered with the St Thomas' Adult Twin Registry in the UK. RESULTS: The overall prevalence of hypermobility was 19.5% in MZ twins and 22.1% in DZ twins. The prevalence of hypermobile joints declined with age, falling from 34% in subjects ages 20-30 years to 18.4% in those ages 60 years or older. Significantly greater concordance for joint hypermobility was observed in the MZ twins when compared with the DZ twins (60% versus 36%), consistent with a genetic influence. In variance components analysis, the age- and body mass index-adjusted heritability of joint hypermobility was estimated to be 70% (95% confidence interval 57-89%). CONCLUSION: Genetic factors have a substantial contribution to joint hypermobility in the adult female population.     

Widespread pain among 11‐year‐old Finnish twin pairs

Objective

To examine the prevalence of widespread musculoskeletal pain (WSP) symptoms in 11‐year‐old Finnish twins and to determine the relative role of genetic and environmental factors in the etiology of WSP.

Methods

Data on current pain items were collected from 1995 to 1998 from a national sample of Finnish families with 11‐year‐old twins born between 1984 and 1987. The presence of WSP was determined using a validated questionnaire method. Pairwise similarity was computed for 583 monozygotic (MZ) pairs, 588 same‐sex dizygotic (DZ) pairs, and 618 opposite‐sex DZ twin pairs. Variance components for genetic and environmental factors were estimated using biometric structural equation modeling techniques.

Results

The prevalence of WSP was 9.9%, with no sex difference. The majority of twin pairs with WSP were discordant. The tetrachoric correlations for male MZ (r = 0.38), male DZ (r = 0.37), female MZ (r = 0.59), female DZ (r = 0.54), and opposite‐sex pairs (r = 0.43) showed little difference by zygosity. Female pairs were more concordant than male pairs among both MZ and DZ twins. Biometric model‐fitting indicated that genetic factors did not account for the pattern of twin similarity. Among boys 35%, and among girls 56%, of the variation in liability to WSP could be attributed to shared familial environmental effects. The remainder was attributed to unshared environmental effects.

Conclusion

Genetic factors seem to play at most a minor role in WSP in 11‐year‐old twins, and environmental factors shared by family members account for a substantial proportion of the variability in WSP.

     

Genetic contribution to individual variation in binocular rivalry rate

Binocular rivalry occurs when conflicting images are presented in corresponding locations of the two eyes. Perception alternates between the images at a rate that is relatively stable within individuals but that varies widely between individuals. The determinants of this variation are unknown. In addition, slow binocular rivalry has been demonstrated in bipolar disorder, a psychiatric condition with high heritability. The present study therefore examined whether there is a genetic contribution to individual variation in binocular rivalry rate. We employed the twin method and studied both monozygotic (MZ) twins (n = 128 pairs) who are genetically identical, and dizygotic (DZ) twins (n = 220 pairs) who share roughly half their genes. MZ and DZ twin correlations for binocular rivalry rate were 0.51 and 0.19, respectively. The best-fitting genetic model showed 52% of the variance in binocular rivalry rate was accounted for by additive genetic factors. In contrast, nonshared environmental influences accounted for 18% of the variance, with the remainder attributed to measurement error. This study therefore demonstrates a substantial genetic contribution to individual variation in binocular rivalry rate. The results support the vigorous pursuit of genetic and molecular studies of binocular rivalry and further characterization of slow binocular rivalry as an endophenotype for bipolar disorder.     

Heritability of lung disease severity in cystic fibrosis

RATIONALE: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. OBJECTIVES: To quantify the contribution of modifier genes to variation in CF lung disease severity. METHODS: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV(1) within the last year was used for cross-sectional analysis. FEV(1) measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (approximately 100% gene sharing) with that of dizygous (DZ) twins/siblings (approximately 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. MEASUREMENTS AND MAIN RESULTS: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82-0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50-0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). CONCLUSIONS: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype.     

Evidence for a major role of heredity in Graves' disease: a population-based study of two Danish twin cohorts

The etiology of Graves' disease (GD), affecting up to 2% of a population in iodine-sufficient areas, is incompletely understood. According to current thinking, the development of GD depends on complex interactions among genetic, environmental, and endogenous factors. However, the relative contributions of the genetic and environmental factors remain to be clarified. In this study we report probandwise concordance rates for GD in a new cohort of same sex twin pairs born between 1953 and 1976 (young cohort), ascertained from the nationwide population-based Danish Twin Register. To elucidate the magnitude of the genetic and environmental influence in the etiology of GD, these new twin data were pooled with our previously published twin data on GD (old cohort). The old cohort consisted of 2338 same sex twin pairs born between 1870 and 1920 who had participated in questionnaire surveys during the 1950s, 1960s, and 1970s. The young cohort included 6628 same sex twin pairs born between 1953 and 1976 who had participated in a questionnaire survey in 1994. In the young cohort there were four monozygotic (MZ) pairs and one dizygotic (DZ) pair concordant for clinically overt GD, giving an overall probandwise concordance rate of 0.35 [95% confidence interval (CI), 0.16--0.57] for MZ pairs and 0.07 (95% CI, 0.01--0.24) for DZ pairs (P < 0.02). In the combined twin cohorts there were eight MZ pairs and one DZ pair concordant for clinically overt GD, giving a crude concordance rate of 0.35 (95% CI, 0.21--0.50) for MZ pairs and 0.03 (95% CI, 0.01--0.12) for DZ pairs (P < 0.02). Model-fitting analysis on the pooled twin data showed that 79% of the liability to the development of GD is attributable to genetic factors. Individual specific environmental factors not shared by the twins could explain the remaining 21%. In conclusion, our study strongly supports the idea that genetic factors play a major role in the etiology of GD and suggest that a further search for susceptibility genes is worthwhile.     

A twin study of erectile dysfunction

BACKGROUND: The extent of genetic influence on erectile dysfunction (ED) is unknown. This study determines the contribution of heredity to ED in a sample of middle-aged men. METHODS: A classical twin study was conducted in the Vietnam Era Twin Registry, a national sample of male-male pairs (mean birth year, 1949) who served on active duty during the Vietnam era (1965-1975). A 1999 male health survey was completed by 890 monozygotic (MZ) and 619 dizygotic (DZ) pairs. The prevalence and heritability of 2 self-report indicators of ED, difficulty in having an erection and in maintaining an erection, are estimated. RESULTS: The prevalence of difficulty in having an erection is 23.3% and in maintaining an erection is 26.7%. Twin correlations for dysfunction in having an erection are 0.35 (95% confidence interval [CI], 0.28-0.41) in MZ and 0.17 (95% CI, 0.09-0.27) in DZ pairs. For dysfunction in maintaining an erection, the twin correlations in MZ and DZ pairs are 0.39 (95% CI, 0.32-0.45) and 0.18 (95% CI, 0.09-0.27), respectively. The estimated heritability of liability for dysfunction in having an erection is 35% and in maintaining an erection is 42%. The heritable influence on ED remained significant after adjustment for ED risk factors. CONCLUSIONS: The present study demonstrates an ED-specific genetic component that is independent of genetic influences from numerous ED risk factors. The results suggest that future molecular genetic studies to identify ED-related polymorphisms are warranted.     

Genetic Predisposition to Organ-Specific Endpoints of Alcoholism

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z., and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per l,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism—26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis—17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis—16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.000l). Maximum-likelihood modeling indicated that ～50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.     

Genetic factors in bone turnover

Genetic factors are major determinants of adult bone density, however, it is unknown how these effects may be mediated. Since bone mineral density is the net result of bone formation and bone resorption we studied biochemical indices of bone formation (serum osteocalcin) and resorption [fasting urinary calcium:creatinine (Ca/Crt) and hydroxyproline:creatinine (OH/Crt)] in adult female twins; 39 monozygotic (MZ) and 31 dizygotic (DZ) twin pairs (age, mean +/- SEM, MZ: 51.1 +/- 1.5 yrs; DZ: 46.5 +/- 1.5 yrs, P = NS). Of these subjects, 18 MZ twin pairs and 10 DZ twin pairs were postmenopausal. The MZ twin pair correlations (rMZ) for each index of bone turnover exceeded that between DZ pairs (rDZ), but this difference was only significant for osteocalcin (rMZ = 0.81, rDZ = 0.21, P less than 0.001). Similarly, in the postmenopausal group examined alone, the rMZ (r = 0.84) for serum osteocalcin was significantly greater than rDZ (r = -0.003, P less than 0.03). These osteocalcin data imply that 80% of the variance in serum osteocalcin could be explained by genetic factors. Although genetic effects on fasting urinary hydroxyproline:creatine and calcium:creatinine were not demonstrable, these indices may be less precise and specific. The data indicate that circulating osteocalcin, and therefore bone formation, is strongly genetically determined. These studies suggest at least one of the mechanisms of the genetic effect on bone mass relates to the regulation of bone turnover.     

Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins

We measured asthma in the last 12 mo, diagnosed by a respiratory physician at interview; atopy, defined by a positive skin prick test to any of eight common allergens; and bronchial hyperresponsiveness (BHR) to hypertonic saline, in 381 twin pairs aged 8 to 18 yr selected from the Australian Twin Registry-183 monozygous (MZ) and 198 dizygous (DZ). The associations between twins, as measured by an odds ratio, were greater in MZ pairs compared with DZ pairs for asthma: 25.6 (95% confidence interval 11.3- 57.8) versus 1.9 (1.0-3. 5); atopy: 14.6 (7.1-30.1) versus 2.5 (1.4- 4.5); and BHR: 14.1 (6. 4-31.0) versus 4.2 (2.1-8.6) (all p < 0.002). The associations between each pair of traits within an individual were slightly greater than the association between one trait in a twin and the other trait in the cotwin (cross-trait cross-pair) in MZ pairs. Further, the associations in MZ pairs were greater than in DZ pairs (p < 0.05). Under the assumptions of the classic twin model, these data suggest that the strong cross-sectional associations between these three traits are due to an overlap between the genetic factors involved in each of these three traits.     

Genetic influences on F cells and other hematologic variables: a twin heritability study

To assess the relative contribution of genetic factors in the variation of F cells (FC) and other hematologic variables, we conducted a classical twin study in unselected twins. The sample included 264 identical (monozygotic [MZ]) twin pairs and 511 nonidentical (dizygotic [DZ]) same-sex twin pairs (aged 20 to 80 years) from the St. Thomas' UK Adult Twin Register. The FC values were distributed continuously and positively skewed, with values ranging from 0.6% to 22%. FC values were higher in women than in men and decreased with age, with the variables accounting for 2% of the total FC variance. The intraclass correlations of FC values were higher in MZ (rMZ = 0.89) than in DZ (rDZ = 0.49) twins. The XmnI-(G)gamma polymorphism in the beta-globin gene cluster had a significant effect on FC levels, accounting for approximately 13% of the total FC variance. Variance components analysis showed that the FC values were accounted for predominantly by additive genetic and nonshared environmental influences, with an estimate of heritability of 0.89. Hemoglobin levels and red blood cell, white blood cell, and platelet numbers were also substantially heritable, with heritability estimates of 0.37, 0.42, 0.62, and 0.57, respectively. Previously, studies of sib pairs with sickle cell disease and isolated family studies showed that high levels of Hb F and FC tend to be inherited. Here, our classical twin study demonstrated that the variance of FC levels in healthy adults is largely genetically determined. (Blood. 2000;95:342-346)     

Evidence of Genetic Predisposition to Alcoholic Cirrhosis and Psychosis: Twin Concordances for Alcoholism and Its Biological End Points by Zygosity among Male Veterans

Medical histories of the 15,924 male twin pairs in the National Academy of Sciences-National Research Council Twin Registry were examined to determine, within pairs, concordances for alcoholism and its medical end points. Prevalences per 1,000 among individual twin subjects were 29.6 for alcoholism, 4.1 for alcoholic psychosis, 14.2 for liver cirrhosis, and 2.1 for pancreatitis. Prevalences were similar for monozygotic (MZ) and dizygotic (DZ) twins. Prevalences in percent among co-twins of diagnosed subjects, that is case-wise twin concordance rates, were, respectively, by diagnosis: alcoholism: 26.3 (MZ), 11.9 (DZ); alcoholic psychosis: 21.1 (MZ), 6.0 (DZ); and liver cirrhosis: 14.6 (MZ), 5.4 (DZ). No twin pairs concordant for pancreatitis were found.
The greater concordance for alcoholic psychosis and for liver cirrhosis among MZ than DZ twins could not be explained by the difference in alcoholism concordance between them. The difference in concordance between MZ and DZ twins persisted when, in addition, it was assumed that only half of the actually occurring cases of alcoholism and of each of the end points have been ascertained. These results provide evidence in favor of genetic predisposition to organ-specific complications of alcoholism and should serve to stimulate searches for the underlying biochemical mechanisms.     

Genetic factors and susceptibility to falls in older women

OBJECTIVES: To determine whether genetic influences account for individual differences in susceptibility to falls in older women. DESIGN: Prospective twin cohort study. SETTING: Research laboratory and residential environment. PARTICIPANTS: Ninety-nine monozygotic (MZ) and 114 dizygotic (DZ) female twin pairs aged 63 to 76 from the Finnish Twin Cohort study. MEASUREMENTS: The participants recorded their falls on a calendar for an average+/-standard deviation of 344+/-41 days. Reported falls were verified via telephone interview, and circumstances, causes, and consequences of the fall were asked about. RESULTS: The total number of falls was 434, of which 188 were injurious; 91 participants had two or more falls. Casewise concordance was 0.61 (95% confidence interval (CI)=0.49-0.72) for MZ twins and 0.49 (95% CI=0.37-0.62) for DZ twins for at least one fall, 0.38 (95% CI=0.23-0.53) for MZ and 0.33 (95% CI=0.17-0.50) for DZ twins for at least one injurious fall, and 0.43 (95% CI=0.26-0.60) for MZ and 0.36 (95% CI=0.17-0.55) for DZ twins for recurrent falls. On average, the proportion of familial influences accounting for the individual differences in susceptibility to at least one fall was 30% and to recurrent falls was 40%; nongenetic familial and nonfamilial factors alone accounted for susceptibility to at least one injurious fall. CONCLUSION: In community-dwelling older women, familial factors underlie the risk of falling but not the risk of injurious falls.     

Twin concordance and sibling recurrence rates in multiple sclerosis

Size and ascertainment constraints often limit twin studies to concordance comparisons between identical and fraternal twins. Here we report the final results of a longitudinal, population-based study of twins with multiple sclerosis (MS) in Canada. Bias was demonstrably minimized, and an estimated 75% of all Canadian MS twin pairs were ascertained, giving a sample sufficiently large (n = 370) to permit additional informative comparisons. Twinning was not found to affect prevalence, and twins with MS did not differ from nontwins for DR15 allele frequency nor for MS risk to their siblings. Probandwise concordance rates of 25.3% (SE +/- 4.4) for monozygotic (MZ), 5.4% (+/-2.8) for dizygotic (DZ), and 2.9% (+/-0.6) for their nontwin siblings were found. MZ twin concordance was in excess of DZ twin concordance. The excess concordance in MZ was derived primarily from like-sexed female pairs with a probandwise concordance rate of 34 of 100 (34 +/- 5.7%) compared with 3 of 79 (3.8 +/- 2.8%) for female DZ pairs. We did not demonstrate an MZ/DZ difference in males, although the sample size was small. We observed a 2-fold increase in risk to DZ twins over nontwin siblings of twins, but the difference was not significant.