SEARCH · PubMed Health

Results for “Multifactorial Inheritance”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources

PubMed2002

Preeclampsia: a multifactorial disease resulting from the interaction of the feto-maternal HLA genotype and HCMV infection.

PROBLEM: To clarify the possible influence of human leukocyte antigen (HLA) mother-child genotypes and human cytomegalo virus (HCMV) presence on the development of preeclampsia. METHODS OF STUDY: One hundred and four DNA samples from mothers with preeclampsia, mothers with a normal history of pregnancies and their neonates were tested by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) for HLA-A, -G, -DRB1, -DQA1, -DQB1 alleles. The HCMV sequences were analyzed using a PCR-SSOP method and the four primers described by Chou (Chou S: J Clin Microb 1992; 30:2307-2310). RESULTS: Compared with their respective controls, a significant increase of DRB1*07 among neonates (P(c) = 0.05) and of DRB1*07 and/or DRB1*06 among pre-eclamptic mothers (P(c) = 0.003, RR = 8,5) was found. When HCMV sequences were detected in pre-eclamptic mothers carrying those phenotypes the RR increased up to 40. Furthermore, the fetal inheritance of a maternal HLA-G*0104 increased the risk for the appearance of the disease (RR = 30; P = 0.025). CONCLUSION: The results suggest that the presence of alleles HLA-G*0104, DRB1*07/06, HCMV sequences and the fetal inheritance of maternal G*0104, should be considered as conditioning factors for the development of preeclampsia.

Alleles↗

PubMed1999

The natural history of the obese strain of chickens--an animal model for spontaneous autoimmune thyroiditis.

Chickens of the Obese strain (OS) are hereditarily affected with spontaneous autoimmune thyroiditis that resembles Hashimoto's thyroiditis of humans in clinical, histopathological, serological, and endocrinological aspects. In this review, the natural history of the OS, reflecting the development and maintenance of the stock and its improvement of productivity over many years at Cornell University, is summarized. To underline the value and usefulness of this animal model, the concept of the multifactorial pathogenesis of autoimmune diseases, which was mainly established at the University of Innsbruck, Austria, is briefly outlined. This detailed analysis on the natural history of the OS was only made feasible by the availability of four decades of records on this chicken line at Cornell University. The report starts with the initial occurrence of a few pullets within the Cornell C-strain (CS) flock that showed obesity, long and silky feathers, and small body size, which, therefore, caused these birds to look notably different than the other CS birds. Experimental findings indicated an autoimmune basis for these characteristics, and the objectives of matings were initially focused on increasing the number of obese individuals for studies on the etiopathology and the mode of inheritance. In subsequent years, matings were directed toward increasing the penetrance and severity of the obese trait in the population. In recent years, the reproductive capability of the obese stock was improved by mating only the best breeders of the population in terms of body weight, egg weight, egg production, fertility, hatchability, and the expression of the obese phenotype. Housing conditions for OS chickens at Cornell and the qualification standards and selection procedures for breeders are described in detail, and results of blood typings are shown. A specific recent finding in OS hens is the high incidence of residues of the right Mullerian duct with cyst formation.

Animal Husbandry↗

PubMed2000

Genetic aspects of miscarriage.

Fetal chromosome abnormalities account for about 50% of first-trimester pregnancy losses. Most of these abnormalities are numerical abnormalities (86%) and a low percentage is caused by structural abnormalities (6%) or other genetic mechanisms, including chromosome mosaicism (8%). The recurrence risk of numerical abnormalities is low, so karyotyping of fetal material in case of a miscarriage does not seem worthwhile in daily practice. Half of the structural abnormalities may be inherited from a parent carrying a balanced chromosome translocation or inversion. Parental carriership is found in 4-6% of the couples with recurrent miscarriage. In case of parental carriership of a balanced structural chromosome abnormality, a next pregnancy may result in a child with an unbalanced structural chromosome abnormality. This child can have multiple congenital malformations and/or a mental handicap. Prenatal diagnosis is therefore recommended. Conventional laboratory techniques, such as tissue culturing and karyotyping, or (semi-)direct chromosome technique of chorionic villi, and the recently developed laboratory techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), are described successively. Until now, not enough evidence has been available about the role of other genetic mechanisms, such as single-gene abnormalities, uniparental disomy, genomic imprinting, multifactorial disorders and skewed X chromosome, in the occurrence of miscarriages.

Abortion, Spontaneous↗

PubMed2005

Mapping gene activity in complex disorders: Integration of expression and genomic scans for multiple sclerosis.

Genetic predisposition contributes to the pathogenesis of most common diseases. Genetic studies have been extremely successful in the identification of genes responsible for a number of Mendelian disorders. However, with a few exceptions, genes predisposing to diseases with complex inheritance remain unknown despite multiple efforts. In this article we collected detailed information for all genome-wide genetic screens performed to date in multiple sclerosis (MS) and in its animal model experimental autoimmune encephalomyelitis (EAE), and integrated these results with those from all high throughput gene expression studies in humans and mice. We analyzed a total of 55 studies. We found that differentially expressed genes (DEG) are not uniformly distributed in the genome, but rather appear in clusters. Furthermore, these clusters significantly differ from the known heterogeneous organization characteristic of eukaryotic gene distributions. We also identified regions of susceptibility that overlapped with clusters of DEG leading to the prioritization of candidate genes. Integration of genomic and transcriptional information is a powerful tool to dissect genetic susceptibility in complex multifactorial disorders like MS.

Animals↗

PubMed1997

Genetics of intracranial aneurysms.

The etiology and pathogenesis of intracranial aneurysms are clearly multifactorial, with genetic factors playing an increasingly recognized role. Intracranial aneurysms have been associated with numerous heritable connective tissue disorders, which account for at least 5% of cases. Of these disorders, the most important are Ehlers-Danlos syndrome Type IV, Marfan's syndrome, neurofibromatosis Type 1, and autosomal dominant polycystic kidney disease; the association with intracranial aneurysms, however, has been firmly established only for polycystic kidney disease. Familial intracranial aneurysms are not rare but account for 7 to 20% of patients with aneurysmal subarachnoid hemorrhage and are generally not associated with any of the known heritable connective tissue disorders. First-degree relatives of patients with aneurysmal subarachnoid hemorrhage are at an approximately fourfold increased risk of suffering ruptured intracranial aneurysms, compared to the general population. Various possible modes of inheritance have been identified in families with intracranial aneurysms, suggesting genetic heterogeneity. Although the benefits have never been quantified, screening for asymptomatic intracranial aneurysms should be considered in families with two or more affected members. The yield of such a screening program may approximate 10%. Although it is unlikely that there is a single gene with major effect, much effort is currently being directed at locating intracranial aneurysm genes.

Connective Tissue Diseases↗

PubMed1998

Familial intracranial aneurysms.

We describe a 53-year-old mother and a her 34-year-old son who suffered from spontaneous subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage due to a ruptured intracranial aneurysm. Diagnosis of the intracranial aneurysm was made by CT scan of the brain, and cerebral angiography. These two cases received surgical intervention and returned to their previous social activity after discharge, even though the mother had arrived in a comatose condition. The literature is reviewed and the characteristic expressions of familial intracranial aneurysms are described. The etiology of cerebral aneurysms is still uncertain but it is likely multifactorial. For the 176 patients with intracranial aneurysm(s) treated at Kaohsiung Medical College Hospital, the mean age at diagnosis was 51.9 years and these aneurysms were distributed mainly at the internal carotid artery (43.8%) and the anterior communicating artery (33.5%). The familial aneurysms tend to rupture at a younger age, occur less often at the anterior communicating artery and more often at the internal carotid artery and the middle cerebral artery as compared with that of non-familial aneurysms. In siblings, aneurysms occur at identical sites or at mirror sites and rupture within the same decade of life twice as frequently as expected in non-familial aneurysm cases. The familial aggregation of intracranial aneurysms and the above characteristic expressions suggest that heredity may play a role in some familial aneurysms. The pattern of inheritance, however, has not been established. Screening examinations and the treatment of unruptured intracranial aneurysms in asymptomatic relatives of the familial cases are also discussed.

Adult↗

PubMed2002

Polymorphism in codons 10 and 25 of the transforming growth factor-beta 1 (TGF-beta1) gene in patients with invasive squamous cell carcinoma of the uterine cervix.

Transforming growth factor-beta 1 (TGF-beta1) has a multifactorial role in the development of cervical cancer. It potently inhibits the growth of epithelial cells that harbour oncogenic human papilloma viruses (HPVs). TGF-beta1 also inhibits the expression of the early viral transforming regions E6 and E7, which appear to be the key oncoproteins. It has been suggested that squamous cell carcinomas are devoid of TGF-beta1, raising the possibility that elevated levels of this growth factor could protect against cervical cancer. It is also recognized that the production and levels of TGF-beta1 are genetically predetermined and individually variable. Two genetic polymorphisms in the DNA encoding the leader sequence of the TGF-beta1 gene have been described and shown to be associated with the production of high or low TGF-beta1 levels in vivo and in vitro. We hypothesized that the inheritance of these polymorphisms could influence the development of invasive cervical cancer. This hypothesis was investigated by studying polymorphism in codons 10 and 25 of the TGF-beta1 gene. We studied 97 patients with invasive cervical cancer and 73 healthy controls and found that the distributions of alleles T (Leu) and/or C (Pro) and alleles G (Arg) and/or C (Pro) in codons 10 and 25, respectively, were similar. There was no significant association between the alleles and the histological degree of cancer differentiation. It appears that the role of this growth factor in cervical oncogenesis is not related to the point mutations that we examined in codons 10 and 25 of the TGF-beta1 gene. We speculate that other factors, including additional polymorphisms of the TGF-beta1 gene, the status of TGF-beta1 receptors, the complex cytokine network, differential responsiveness of cells to the stimuli, and the status of the precancer/cancer genome, may play a role in development of invasive cervical cancer.

Adult↗

PubMedDate not supplied

A Japanese adult case of cystic fibrosis causing bone demineralization.

Cystic fibrosis is an inherited, multisystem disorder characterized by an abnormality in exocrine gland function. It leads to chronic pulmonary disease in most cases and pancreatic insufficiency in 85 percent of patients. Although this disease is not uncommon in Caucasians, it has been considered very rare among Japanese. The majority of patients are diagnosed in infancy or childhood. The patient in this case report was a 45-year-old Japanese man who had not been diagnosed as having cystic fibrosis. This patient had recurrent episodes of pulmonary infection that started in childhood, and plain films of the chest showed increased interstitial markings, hyperaeration, and bronchiectasis. CT of the upper abdomen showed a generally enlarged pancreas with complete fatty replacement. Serum and urine pancreatic enzyme levels were low, suggesting pancreatic insufficiency. Repeated sweat tests were positive. A roentgenologic skeletal survey showed general demineralization, which may be multifactorial. In this case, it was concluded that vitamin D deficiency caused by vitamin D malabsorption and/or insufficient sunlight exposure was mainly responsible for the demineralization and that chronic respiratory acidosis might also be partially responsible.

Bone and Bones↗

PubMed2000

The genetic heterogeneity of "schizophrenia".

The main reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. This has not changed markedly following the introduction of modern operational diagnostic systems. Taking schizophrenia as a disease entity or assuming schizophrenia spectrum psychoses to represent a continuum of diseases without any clear dividing lines, the results of family and twin studies point to a multifactorial etiology based on a polygenic mode of transmission. Further, then it has to be assumed a familial continuum from schizophrenia to affective psychosis and other spectrum disorders. However, in family and twin studies based on Leonhard's classification, there is clearcut evidence that schizophrenic spectrum psychoses have to be divided into clinical and etiological subgroups with a completely different genetic background. For example, systematic catatonia is, for the most part, a sporadic disease, whereas periodic catatonia aggregates in families in a manner consistent with a major gene effect. Further, the results indicate that schizophrenic spectrum psychoses consist of three main valid categories: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias. In the case of cycloid psychosis and systematic schizophrenias, genetic loading seem to be very low, while "environmental" factors, for example, birth complications, may play an important etiological role. Unsystematic schizophrenias, however, are predominantly inherited and "environmental" factors are not very prominent.

Adult↗

PubMed2000

Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood Institute Family Heart Study.

OBJECTIVE: Considering that waist-to-hip ratio (WHR) is a simple anthropometric measure of obesity and is a better predictor of coronary heart disease than body mass index (BMI), the genetic underpinnings of WHR are of interest. The inheritance pattern of WHR, before and after adjustment for BMI (WHR-BMI), was investigated in 2713 individuals from 1038 nuclear families in the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI-FHS). RESEARCH METHODS AND PROCEDURES: Waist and hip measurements were taken twice, and the means of the measurements were used to calculate the WHR. Adjustments for age were carried out separately by sex, using stepwise multiple regression procedures for WHR and WHR-BMI phenotypes. Segregation analysis was applied using the unified model as implemented in the computer program POINTER. RESULTS: For age-adjusted WHR, the segregation results suggested an additive major gene that accounts for 35% of the phenotypic variance, and approximately 30% of the sample are homozygous for the "high" genotype. The results for age- and BMI-adjusted WHR were also compatible with a major gene; however, the multifactorial model provided the most parsimonious fit to the data. DISCUSSION: Although the genetic mechanisms for several obesity traits have been studied, tests of Mendelian segregation on this simple anthropometric measure (WHR) have not been reported previously. This study provides evidence for the presence of a major gene for age-adjusted WHR, suggesting that it is an appropriate trait for further genetic analysis, especially because it has strong predictive value and probably relates biologically to cardiovascular risk.

Body Constitution↗

PubMed2000

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗

PubMed2000

Pathophysiology of primary hyperparathyroidism.

Parathyroid gland is the overall regulatory organ within the systemic calcium homeostasis. Through cell surface bound calcium-sensing receptors external calcium inversely regulates release of parathyroid hormone (PTH). This mechanism, which is voltage independent and most sensitive around physiologic calcium concentrations, is regulated through a 120 kDa calcium sensing receptor, CaR. Inherited inactivation of this receptor is the cause for familial hypocalciuric hypercalcemia (FHH). Parallel research identified the 550 kDa glycoprotein megalin, which also is expressed on the parathyroid cell surface, as another potential calcium sensing protein. Although this protein expresses numerous calcium binding sites on its external domain, its main function may be calcium sensitive binding and uptake of steroid hormones, such as 25-OH-vitamin D3 (bound to vitamin D binding protein) and retinol. In hyperparathyroidism (HPT), excessive PTH is secreted and the calcium sensitivity of the cells reduced, i.e. the set-point, defined as the external calcium concentration at which half-maximal inhibition of PTH release occurs, shifted to the right. Pathological cells have reduced expression of both CaR and megalin, and reduced amount of intracellular lipids, possibly including stored steroid hormones. A number of possible genetic disturbances have been identified, indicating multifactorial reasons for the disease. In postmenopausal women, however, the individual group with highest incidence of disease, a causal relation to reduced effect of vitamin D is possible. An incipient renal insufficiency with age, lack of sunshine in the Northern Hemisphere, and an association to the baT haplotype of the vitamin D receptor supports this theory. This review summarizes data on regulation of PTH release, dysregulation in HPT, as well as proliferation of parathyroid cells.

Animals↗

PubMed1984

Genetic aspects of "uncomplicated" hydrocephalus and its relationship to neural tube defect.

Congenital hydrocephalus is a relatively uncommon abnormality in population malformation surveys accounting for between four and ten out of every 10,000 births. In 30%, it is caused by aqueduct stenosis. The majority of cases have a multifactorial aetiology, the genetic component, which is polygenic, rendering the developing foetus susceptible to largely unidentified environmental factors in early development. Some cases are caused by single gene defects. Family studies suggest that the risk to siblings of a child with uncomplicated congenital hydrocephalus, where the anatomical site is not specified, is about 1 in 50 (1 in 40 for males, 1 in 80 for females). With aqueduct stenosis, the risk to brothers of affected boys is 1 in 22, to sisters only 1 in 50. The risks to siblings of sisters is less. Probably less than 2% of uncomplicated hydrocephalus has an X-linked basis and such an aetiology should be suspected if the special clinical features are present, there is more than one male sibling affected, or there are affected male relatives on the mother's side. Dandy-Walker's syndrome may be recessively inherited and there are some other, but very rare, monogenic causes for hydrocephalus. There is not obvious additional risk for neural tube defect. Non-directive genetic counselling should be given either at the genetic clinic or at a specially arranged clinic appointment and should include not only the risk to the family members, but also the options for avoiding recurrences, and any prenatal diagnostic tests available, such as high precision ultrasonography and a serum alphafetoprotein estimation at about sixteen weeks gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Aqueduct↗

PubMedDate not supplied

Genes and gastric cancer.

Gastric cancer remains quite a common malignancy and counts among the most important causes of cancer-related death worldwide. Although the pathogenesis is multifactorial, familial aggregation in a significant proportion of cases suggests the importance of genetic predisposition. The association between the E-cadherin/CDH1 gene germline mutations and the development of diffuse gastric cancer was the first evidence for a molecular basis of gastric cancer in predisposed families and led many authorities in the world to produce guidelines regarding the management of such families members. The recent advances in genetics resulted in the discovery of numerous genetic events occurring during the course of gastric carcinogenesis (activation of oncogenes, silencing of tumor suppressor genes, mutations in DNA-repairing genes) and contributed to a better understanding in pathogenesis. Many genetic changes described have been found to affect tumor's biological behavior. In this article the authors attempt a review of all the molecular alterations in gastric cancer described in the literature and their impact on the management of patients with an inherited predisposition to gastric cancer. The promising role of gene therapy in the treatment of gastric cancer in the near future is also commented on.

Cadherins↗

PubMed1978

Hyperinsulinemia in obesity syndromes: its metabolic consequences and possible etiology.

Animal models with genetic or experimentally produced (lesions of hypothalamus) obesities are numerous and unlikely to ever be reduced to a single pathophysiologic entity. However, obese animals have many similar traits in common. They are all hyperinsulinemic, an abnormality that occurs early in the development of these syndromes and appears to be of prime importance in producing most of the metabolic changes observed both in the early and late phases of the obesity syndromes. In all instances, obesity is an evolutional syndrome in which the early phase is different from the later one. The early phase is principally characterized by increased hepatic very low density lipoprotein (VLDL) output, increased adipose tissue lipogenesis and VLDL uptake, hence, increased fat accretion and fat cell size. These abnormalities are secondary to hyperinsulinemia and can be reversed toward normal by normalizing circulating insulin levels. The late phase is characterized by the continuation of the disorders of the early one plus a superimposed abnormality, the insulin resistance state, that is detectable particularly at the level of adipose and muscle tissues, and eventually brings about hyperglycemia. Insulin resistance is a multifactorial pathological condition that includes at least: (a) a decrease (more or less marked) in insulin binding to target tissues that is responsible for the decrease in tissue sensitivity to the hormone; (b) intracellular defects that are probably responsible for the decreased insulin responsiveness of target tissues. The origin of hyperinsulinemia in animal obesities is still ill-defined. Lesions of the ventromedial hypothalamus (VMH) produce rapid and lasting hyperinsulinemia. Such lesions produce, in addition, increased secretion of insulin and glucagon and changes in pancreatic insulin, glucagon, and somatostatin content in subsequently perfused pancreases. The locus responsible for these effects is not defined and may actually involve a series of interrelated loci. Whatever the latter may be, one of the routes of CNS influence upon endocrine pancreas is the vagus nerve, although a humoral factor has also been claimed. The etiology of hyperinsulinemia in genetically obese animals is unknown. Genetic inheritance could bear primarily upon some hypothalamic or other CNS sites, with secondary alterations in the endocrine pancreas function, or primarily on the islets of Langerhans with possible alteration in the respective function of the A, B, and D cells with resulting excessive insulin secretion.

Animals↗

PubMed1982

Mitotic index in mouse embryos with 6-aminonicotinamide-induced and inherited cleft lip.

Three types of cleft lip were studied histologically before and during lip formation in mouse embryos. C57BL/6 embryos observed near term following treatment with 6-aminonicotinamide (6AN) at gestation D9/12 (vp day = day 0) had 18% median cleft lip. Treated embryos observed at D10 and D11 showed retarded somite and nasal placode development. Sections at lip closure time showed marked reduction of medial and some reduction of lateral nasal processes, and the mitotic index was significantly reduced in the nasal area on D10 and D11 but less consistently in the neural area. 6AN-treatment on D10/8, caused 22% lateral cleft lip. Treated embryos showed initial retardation of somite and nasal placode development that became normal by D11/14. Sections showed reduction of the medial and lateral nasal processes, and less organized denser nasal ectoderm. The mitotic index was significantly reduced in the nasal and neural areas on D10 and D11. In crosses having the major gene mutation dancer (Dc) 20% of embryos had lateral cleft lip and potential cleft lip mutant embryos showed reduced lateral and medial nasal processes. Mitotic index was not reduced in the nasal area but it was in the neural area. The CL/Fr strain, with a predisposing face shape in which 26% of the embryos have cleft lip of multifactorial origin, had a mitotic index similar to that of C57BL/6 (0% cleft lip) at lip closure time, D11/14, and prominent medial nasal processes. It is postulated that 6AN-induced median cleft lip is due to reduced cell proliferation in and size of the medial nasal processes; 6AN-induced lateral cleft lip to reduced cell proliferation and reduced medial and lateral nasal processes and dancer lateral cleft lip to reduction of the medial nasals.

6-Aminonicotinamide↗

PubMed2004

No association between variation of the FOXP3 gene and common type 1 diabetes in the Sardinian population.

Mutations of the forkhead/winged helix transcription factor FOXP3 gene on chromosome Xp11.23 cause a rare recessive monogenic disorder called IPEX (immune dysregulation, polyendocrinopathy, including type 1 diabetes, enteropathy, and X-linked syndrome). FOXP3 is necessary for the differentiation of a key immune suppressive subset of T-cells, the CD4+CD25+ regulatory T-cells. Previously, we reported a significant male-female bias in the common, multifactorial form of type 1 diabetes in Sardinia and evidence of linkage of chromosome Xp11 to the disease. These findings indicate that FOXP3 is a prime functional and positional candidate locus for the common form of type 1 diabetes. In the present study, we initially scanned 82 kb of the FOXP3 region for common polymorphisms, including sequencing all of the coding and functionally relevant portions of the gene in 64 Sardinian individuals. Then the most informative polymorphisms in 418 type 1 diabetic families and in 268 male case and 326 male control subjects were sequentially genotyped and tested for disease association. There is no evidence that variants in the FOXP3 regions analyzed are associated with type 1 diabetes and account for the male-female bias observed in Sardinia. Our data indicate that allelic variation in or near the coding regions of the FOXP3 gene does not have a major role in the inherited susceptibility to the common form of type 1 diabetes.

Adolescent↗

PubMed1996

Association studies in consanguineous populations.

To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients.

Case-Control Studies↗