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Results for “multifactorial inheritance”

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PubMed1996

[A study on model of inheritance of systemic lupus erythematosus in Chinese].

Analysis of segregation and heritability were performed, with the aid of Penrose's method, maximum likelihood estimation and Falconer's method, in 215 cases with systemic lupus erythematosus (SLE) and their pedigrees to explore its possible model of inheritance. Results showed that prevalence of SLE in first-degree relatives of the proband with SLE was 0.85% and higher than that in general population (0.03%). A ratio of s/q approached 1/square root q with Penrose's method, segregation proportion was equal to 0.029 with simple segregation analysis, with a chi-square for goodness-of-fit of 0.0001 (P > 0.05), and the heritability of SLE was 56.7% (P < 0.05). It suggests that SLE follows a pattern of multifactorial inheritance rather than single-gene one.

Adolescent↗

PubMed1987

A genetic analysis of clubfoot in Hawaii.

The roles of major genes and multifactorial inheritance in the etiology of clubfoot (talipes equinovarus) were investigated based on 365 nuclear families consisting of three major racial groups of Hawaiians, Caucasians, and Orientals in Hawaii. Complex segregation analysis was employed using the mixed model with four parameters: major gene displacement (t), degree of dominance (d), gene frequency (q), and heritability (H). Heterogeneity was evident among the racial groups in the pattern of segregation of clubfoot. The most plausible genetic model is the presence of major gene effects with the multifactorial component for the Hawaiian and Caucasian groups, whereas no major gene action is evident for the Oriental group.

Asian People↗

PubMed1998

Inheritance of chronic tension-type headache investigated by complex segregation analysis.

We investigated the mode of inheritance of chronic tension-type headache in 122 families. The probands were from the Copenhagen Headache Clinic, Denmark. The criteria of the International Headache Society were used. The patterns of segregation of chronic tension-type headache were assessed by complex segregation analysis performed with the computer program POINTER. Of the 122 probands with chronic tension-type headache, 56 had 71 first-degree relatives with chronic tension-type headache. The complex segregation analysis indicates that chronic tension-type headache has multifactorial inheritance.

Age Factors↗

PubMed1987

The spectrum concept of schizophrenia: evidence for a genetic-environmental continuum.

Family data from 84 chronic schizophrenic, 11 schizotypal and 90 normal control probands were analyzed by multivariate-multifactorial genetic models using morbid risk statistics. The results were consistent with multifactorial inheritance whereby chronic schizophrenia and schizotypal personality disorder represent different phenotypic manifestations of the same underlying process; that is, the two disorders were found to have different thresholds on a single continuum of genetic-environmental liability. When subclassified according to Taylor and Abrams' criteria, chronic schizophrenic subjects who met these criteria (narrow schizophrenia) had a higher threshold of liability than those who did not (broad schizophrenia). The hypothesis of separate liabilities for the different disease states was rejected. Overall, the results suggest a gradation in multifactorial liability from schizotypal personality disorder (mild) to broad schizophrenia (moderate) to narrow schizophrenia (severe).

Adult↗

PubMed1992

A critical analysis of data presented in eight studies favouring X-linkage of bipolar illness with special emphasis on formal genetic aspects.

High lod scores were obtained in several X-linkage studies of bipolar illness under the assumption that a subgroup of manic depression follows an X-linked dominant mode of inheritance. We have previously shown that the segregation patterns do not substantiate this assumption. We now statistically address the lack of evidence for X-linked inheritance by sex-dependently analyzing segregation ratios and clinical data presented in eight positive X-linkage studies. Accordingly, affected males have significantly fewer offspring, a lower mean age and a higher bipolar to unipolar ratio than affected females. There are two possible explanations for these findings: either the X-linked subgroup of bipolar illness has unique features that have not been accounted for clinically, or (more probably) the pedigree structures could also (and might be more likely to) result from ascertaining kindreds following autosomal or multifactorial inheritance only, with exclusion of kindreds encompassing male to male transmission.

Adult↗

PubMed1992

[Clinical-genealogic analysis of diaphragmatic hernias].

The results of clinical-genetic examination of 174 probands with congenital diaphragmatic hernias and their families are presented. Genetic heterogeneity of diaphragmatic hernias, the spectrum of inherited syndromes obtained in the present study and shown in literature the spectrum and frequency of congenital malformations accompanying diaphragmatic hernias were shown. No increase in the average age of the probands' parents and in the marriage distances changes was observed both for isolated diaphragmatic hernias and those accompanied by other malformations was observed. Because of the high risk of neural tube defects occurrence in the sibs of children with diaphragmatic hernias, the probands' mothers should be recommended to undergo prenatal diagnosis of their further pregnancies for this character. The evidence of multifactorial inheritance for the most of diaphragmatic hernia cases was obtained. Empirical recurrent risk for probands' sibs was 1.54 + 1.5%.

Abnormalities, Multiple↗

PubMed2001

[Molecular genetic findings in migraine].

This review focuses on the different molecular genetic findings in migraine. Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura, which is inherited as an autosomal dominant. Half the cases of FHM are caused by point mutations in the CACNA1A gene on the short arm of chromosome 19 (19p). The gene encodes a calcium ion channel. Other mutation types cause episodic ataxia 2 (EA-2). Expansions of the CAG repeat in the 3' end bring about spinocerebellar ataxia 6 (SCA 6). Some families with FHM link to loci on the long arm of chromosome 1 (1q). The genes have not yet been identified. Some families neither link to 1q nor to 19p. Population-based family and twin studies have shown that migraine both with and without aura have a multifactorial inheritance. The CACNA1A gene may be of importance for ordinary forms of migraine in a few families. Mutations in genes on the X chromosome, dopamine receptor genes, and the ACE gene appear to be involved in migraine in a few families, whereas genes for nitric oxide synthase, serotonin receptors, and mitochondrial DNA do not seem to be involved. The positive associations have not been reproduced in other studies and therefore they should be interpreted with care. It is to be hoped that in the next few years much more will be known about the molecular genetic mechanisms of migraine with and without aura. FHM is an ion channel disorder, and many factors suggest that migraine is also an ion channel disorder, which is consistent with the paroxysmal nature of the illness.

Calcium Channels↗

PubMed2006

Genetic epidemiology of vitiligo: a study of 815 probands and their families from south China.

BACKGROUND: Genetic factors are thought to be involved in the development of vitiligo. AIM: To explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients and their families from south China (Zhejiang Province). METHODS: Data for 815 patients with vitiligo were obtained by questionnaire. The inheritance pattern estimation, heritability calculation, and complex segregation analysis were performed using the Penrose method, Falconer regression method, and SAGE-REGTL program, respectively. RESULTS: In 815 vitiligo probands, 128 (15.7%) had a family history. The ratio of the sibling prevalence rate to the population prevalence rate (s/q) approached 1/square root q using the Penrose calculation, and the heritability degrees of vitiligo in the first- and second-degree relatives were 59.6% and 55.2%, respectively. The complex segregation analysis suggested that the dominant model was the best-fit genetic model for vitiligo. CONCLUSIONS: Genetic factors play an important role in the occurrence of vitiligo, and the genetic model of vitiligo in this population is consistent with a polygenetic or multifactorial inheritance in a dominant major gene pattern.

Adult↗

PubMed1984

The genetics of diabetes mellitus, including the South African perspective.

By and large, essential diabetes mellitus is thought to be 50% inherited and 50% environmental. In insulin-dependent diabetes mellitus (IDDM) there is a strong link with the HLA system with regard to the inheritance of 'susceptible' diabetic genes, especially the DR3 and DR4 alleles. In IDDM environmental factors act in a predisposed individual to initiate an immune response with resultant beta-cell damage and destruction. Non-insulin-dependent diabetes mellitus (NIDDM) has no clear HLA link, but has been shown in studies of twins to have a stronger genetic basis than IDDM. In NIDDM environmental factors (race, ethnicity, diet, obesity) have an important influence on the clinical expression of the disease and the severity of complications in a genetically predisposed individual. The non-insulin-dependent diabetes of the young (NIDDY) variant and the phenomenon of chlorpropamide-primed alcohol-induced flushing both underline the heterogeneity of NIDDM. Because of the heterogeneous nature and multifactorial inheritance pattern of diabetes mellitus, accurate genetic counselling is not possible as yet. However, data to date suggest that it is unwise to advise prospective parents not to procreate, since the overall risk of the development of clinical diabetes mellitus is extremely low.

Black People↗

PubMed1988

Inheritance of idiopathic torsion dystonia among Ashkenazi Jews.

The mechanism(s) of inheritance of primary dystonia are unclear. An autosomal recessive form among Ashkenazi Jews and an autosomal dominant form among non-Jews have been proposed. However, the patterns of inheritance, particularly among Ashkenazim, are controversial. In this report we have reviewed the literature particularly as it pertains to the mode of inheritance among Ashkenazim. We also report the results of a pilot study of the families of 25 independently ascertained Ashkenazi probands with onset of primary dystonia before age 27 years. A total of 91/98 living first-degree relatives were examined; of these 91, 86 were greater than or equal to 8 years of age at time of examination and were included in our analysis. Overall, 14/86 (16.3%) of first-degree relatives were affected. We found 11.4% (4/35) of parents, 22.2% (8/36) of siblings, and 13.3% (2/15) of offspring were definitely affected. This finding of an approximately equal risk to parents, siblings, and offspring is consistent with autosomal dominant transmission with a minimum penetrance of 32.6%. Our findings do not support autosomal recessive or multifactorial inheritance.

Adolescent↗

PubMed2005

Complex segregation analysis of nasopharyngeal carcinoma in Guangdong, China: evidence for a multifactorial mode of inheritance (complex segregation analysis of NPC in China).

The striking geographical and ethnic distribution of nasopharyngeal carcinoma (NPC) suggests the involvement of genetic and environmental factors in NPC development. The purpose of this study is to investigate the fit of single gene, polygenic and multifactorial models to the observed pattern of transmission of NPC in a hospital-based family history study conducted by the Cancer Center of Sun Yat-Sen University (CCSYU) in Guangzhou, China. Complex segregation analysis of a total of 1903 Cantonese pedigrees ascertained at CCSYU was conducted using a unified mixed model after the pedigrees were partitioned into 3737 nuclear families. The mixed model assumes that a phenotype is influenced by the additive and independent effect of a major gene, together with multifactorial components (genetic and environmental) and a random environmental effect. The current results do not provide evidence for a major gene and the observed data are best explained by a multifactorial mode of inheritance for NPC.

Adolescent↗

PubMed1993

[Evidence of genetic and environmental factors in manual laterality. Study of 120 Mexican families].

Environmental factors as well as different modes of inheritance has been suggested to explain the etiology of left-handedness. In order to improve knowledge of this problem, manual skill (MS) of parents (n = 234), siblings (n = 506) and children (n = 126) of 60 right-handed (RHI) and 60 left-handed (LHI) index cases (IC), born in Mexico City, were studied. Parents and siblings of both IC had similar frequencies of left-handedness. Quite the contrary, 36.7% of children of LHI were left-handed, while 7.3% children of RHI happen to be left-handed (P < 0.00025). No differences were found in the appearance of perinatal environmental factors. These findings are explained in part according to the pressure exerted by parents and/or teachers for dextrality. The impact of this influence modifies the effect of several unknown genes (multifactorial inheritance). The understanding of the above mechanisms in the etiology of MS is relevant not only for academic purposes, but for the educational sphere as well.

Adolescent↗

PubMed1981

Genetic analysis of the Stanford LRC family study data. I. Structured exploratory data analysis of height and weight measurements.

A new methodology for determining mode for inheritance of continuously distributed traits in nuclear families, structured exploratory data analysis (SEDA), is described and applied to height and weight measurements. The family data were collected as part of the Lipid Research Clinic's collaborative study (LRC) and consists of first degree relatives of Stanford University employees who were selected either as a 2% random sample or were identified through a high lipid value. The variables are all standardized using three methods of age and sex adjustment based on two reference populations. The analysis and interpretations are based on the following statistics and indices: 1) the major gene index (MGI (alpha); 2) two measures of correlations between the midparental value and offspring (MPCC); and 3) the offspring between parent functions (OBP (beta). Consistent with a number of other studies, the results support that height shows multifactorial inheritance while height is principally under the influence of non-genetic environmental factors. In contrast to the random families, the male children of the probands who were selected due to their high lipid values exhibit height measurements which appear to involve environmental components or some major gene concomitants. The difference between the random and high lipid families is supported by all three statistical methods.

Adolescent↗

PubMed2025

Novel Protein-Altering Variants in Cleft Genes Transmitted in Families With NSCL±P.

BACKGROUND: Pathogenic protein-altering variants play a role in the etiology of nonsyndromic cleft lip with or without palate (nsCL±P), one of the most common craniofacial anomalies. However, the genetic basis of many cases remains unclear, complicating risk prediction for affected families. PURPOSE: This study utilized whole-genome sequencing (WGS) of 150 case-families with nsCL±P from sub-Saharan Africa to identify pathogenic risk variants. STUDY DESIGN, SETTING, SAMPLE: This study utilized whole-genome sequencing (WGS) of 150 case-families with nsCL±P from sub-Saharan Africa to identify risk variants. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: Genetic variants. MAIN OUTCOME VARIABLES: Nonsyndromic cleft lip with or without palate (nsCL±P). ANALYSES: Genomes were sequenced at a mean ×30 coverage, and variants were prioritized using CADD (≥20), REVEL (≥0.5), and ACMG/AMP clinical significance criteria. RESULTS: We identified pathogenic protein-altering variants in CHD7 (p.Arg1345His), LRP2 (p.Asp3245Asn), RYR1 (p.Arg2163Leu, p.Pro2903Thr), SHH (p.Met114Val), and WNT3 (p.Ser112Pro) highlighting the role of hedgehog signaling pathway (FDR=5.32e-12) in nsCL±P. These variants were inherited from unaffected parents suggesting an incomplete penetrance of the variant effect. Although mouse data showed that knockout of these genes produces cleft phenotypes, in vivo studies will help us better understand how the consequences of these variants differ from benign mutations. The presence of these protein-altering variants in unaffected parents-incomplete penetrance, provides additional evidence supporting the trait complexity. CONCLUSIONS AND RELEVANCE: This study identified rare, pathogenic protein-altering variants in genes involved in key developmental pathways in African families affected by nsCL±P. These findings highlight the critical role of the hedgehog signaling pathway and related networks in the etiology of nsCL±P. These findings underscore the importance of whole-genome sequencing in genetically diverse populations to uncover novel risk variants. These findings enhance our understanding of the genetic etiology of nsCL±P, particularly in under-represented African populations and support the multifactorial inheritance and the involvement of developmental pathways, such as hedgehog signaling in the etiology of clefting.

Humans↗

PubMed2002

Major gene evidence after MTHFR-segregation analysis of serum homocysteine in families of patients undergoing coronary arteriography.

Elevated levels of homocysteine is a risk factor for coronary artery disease. Polymorphic alleles in the MTHFR genes that cause recessively inherited increased homocysteine level can explain only a small proportion of the observed variation in homocysteine level. To investigate additional genetic influences, we examined environmental, familial, and genetic influences on serum homocysteine levels in 661 family members of 112 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine if an unobserved Mendelian major gene could explain the familial homocysteine distribution. Adjustments for age, lifestyle (smoking and alcohol consumption), serum folate and vitamin B12, and the measured genotype effect of the MTHFR C677T mutation was carried out separately for males and females using multiple regression models for homocysteine, before and after log-transformation prior to this segregation analysis. After excluding the effects of mutations in the MTHFR genes, we found evidence of a major gene acting in a co-dominant manner. Estimated mean homocysteine levels for the three putative genotypes (LL, LH, and HH) were 8.0, 10.1, and 15.9 micro mol/l, respectively, with relative frequencies of 56.8%, 37.2%, and 6%, respectively. Our analysis suggested the presence of a co-dominantly expressed major gene, in addition to the effects of the MTHFR C677T mutation. The results of this study also indicated that multifactorial inheritance was supported more strongly than Mendelian inheritance alone. Our findings may have implications for attempts to identify new homocysteine susceptible genes.

Adolescent↗

PubMed1999

Primary megalencephaly at birth and low intelligence level.

OBJECTIVES: To evaluate the association between primary megalencephaly (PMG) at birth and psychosensory conditions and to determine mother-child similarity for PMG at birth. BACKGROUND: PMG is defined as a head circumference (HC) above the 98th percentile that most likely is due to brain enlargement and is not secondary to disease. Previously, PMG in children was reported to be associated with learning disabilities. Contradictory results regarding an association between PMG and intelligence in children exist. Many believe PMG expressed in childhood and adulthood may be inherited. METHODS: Birth records on HC from 144,273 boys, of whom 732 had PMG, were linked to data concerning intelligence level, mental retardation, and impairment of vision and hearing. A potential association between PMG at birth and mental retardation was also examined in 3,204 mentally retarded boys and girls. Parent-offspring similarity for PMG at birth was determined in 13,585 mother-child pairs. RESULTS: PMG was significantly associated with low intelligence level (odds ratio, 1.32; 95% confidence interval [CI], 1.11 to 1.38). The estimated odds ratio for mental retardation in PMG cases versus controls was 1.31 (95% CI, 0.80 to 2.02). There were no differences in frequencies of vision and hearing impairments between PMG cases and controls. Associations between mother's and child's birth weight-normalized HC (r = 0.14; p<0.0001) and PMG (odds ratio, 2.55; CI, 2.00 to 3.25) were found, supporting a multifactorial inheritance of PMG. CONCLUSIONS: PMG at birth is a risk factor for low intelligence level but not for vision and hearing impairments. The heritability of HC and PMG is moderate.

Adult↗

PubMed1996

Migraine without aura and migraine with aura are inherited disorders.

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicated that both MO and MA have multifactorial inheritance without generational difference.

Adolescent↗

PubMed1976

Intraocular pressure, cup-disc ratio, and steroid responsiveness in retinal detachment.

A review of the literature failed to indicate whether the high incidence of open angle glaucoma in patients with nontraumatic rhegmatogenous retinal detachment is due to common genetic determinants. The diurnal variation of intraocular pressure, the cup-disc C/D ratio, and the intraocular response to topically applied corticosteroids were studied in 30 subjects with unilateral, nontraumatic, rhegmatogenous retinal detachment. The results indicate that 20% of the subjects were high steroid responders and that 53% had a C/D ratio greater than 0.3. We shall discuss the relationship of these findings to the multifactorial inheritance of open angle glaucoma.

Administration, Topical↗