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An epidemiologic investigation of a rubella outbreak among the Amish of northeastern Ohio.

From April 1990 to April 1991, 278 cases of rubella were reported to the Ohio Department of Health. Of these, 276 (99 percent) were among the Amish of northeastern Ohio. The outbreak involved eight counties in an area that contains large settlements of Old Order Amish. Members of this community of Amish frequently take religious exemption from recommended immunization practices and are believed to represent a high proportion of Ohio's rubella-susceptible persons. Vaccination history was known only for 146 of the Amish people. Of those, only four had a positive history of rubella vaccination. Of the 276 Amish with cases of rubella, 65 (24 percent) were younger than age 5 years, 104 (38 percent) were ages 5-14, 46 (17 percent) were ages 15-19, 32 (12 percent) were ages 20-29, 6 (2 percent) were ages 30 or older, and age was not reported for 23 (8 percent). The ratio of males to females with rubella was 1:1. Five women of the Amish community were pregnant; four had been ill with symptoms consistent with rubella. Three were in their first trimester. Congenital rubella syndrome did not occur in any of the four live births. Serology was available for only the two non-Amish people, and both were acute phase serum-positive for Immunoglobulin M.

Adolescent↗

Biocultural approaches to health and mortality in an Old Order Amish community.

The assumption that Amish cultural value of cooperation leads to greater longevity, prosperity and well-being among elders was examined using historical demographic and ethnographic analysis in a conservative Old Order Amish community. Migration, fertility, mortality and morbidity data since 1948 were used to identify population structure. The population pyramid in the Amish community (3% of the population over age 60, compared to 18% of the neighboring non-Amish rural area) is largely determined by natural fertility with low infant mortality. Household ethnography explored health beliefs, access to health care, caregiving patterns, and economic strategies. The perception that community cooperation and altruistic behavior were of benefit to Amish health is supported by mortality rates. Amish age standardized death rates were 19% below the US death rate in 1960. Migrating to form new communities and selectively utilizing acute (but not preventive or public) health care services, emerged as strong cultural patterns that facilitate reproductive success among the Amish.

Anthropology, Cultural↗

Alzheimer's disease and apolipoprotein E-4 allele in an Amish population.

Alzheimer's Disease (AD) is a complex genetic disorder with four loci already identified. Mutations in three of these, the amyloid precursor protein, presenilin I, and presenilin II, cause early-onset AD. The apolipoprotein E (APOE) gene contributes primarily to late-onset AD. The APOE-4 allele acts in a dose-related fashion to increase risk and decrease the age-of-onset distribution in AD. We examined the effect of APOE on AD in a previously unstudied Amish population that has a lower prevalence of dementia compared with other populations. We sampled a large inbred family with 6 late-onset AD members. We also genotyped 53 individuals from the general Amish population as controls for the APOE allele frequency estimates. The frequency of the APOE-4 allele in the Amish controls was 0.037 +/- 0.02. This differed significantly compared with three independent sets of non-Amish white controls (p < 2 x 10(-4), p < 6 x 10(-5), and p < 2 x 10(-6)). In addition, all Amish AD-affected individuals had APOE 3/3 genotypes; no APOE X/4 or 4/4 individuals were observed. We suggest that the lower frequency of dementia in the Amish may be partially explained by the decreased frequency of the APOE-4 allele in this population, and that the inbred nature of this pedigree, with its strong clustering of cases contrasted against the lower frequency of dementia, indicates that additional genetic factors influence late-onset AD.

Adult↗

High-resolution genetic mapping of the cartilage-hair hypoplasia (CHH) gene in Amish and Finnish families.

We recently assigned the gene for cartilage-hair hypoplasia (CHH) to chromosome 9 in Finnish families. Here we have extended and refined our previous linkage analyses by studying 22 Amish and 15 Finnish CHH families and by testing additional markers. The CHH gene maps to 9p in both series and shows no evidence of heterogeneity either within or between the populations. CHH is very closely linked to marker locus D9S163, with no recombinations observed and a combined maximum multipoint lod score of 26.30 for a location at D9S163. Although the odds against a location of the CHH gene between two more distal marker loci, D9S52 and D9S165, are only 48:1, the evidence provided by an observed recombination between the CHH locus and D9S165 and haplotype data at D9S165 and D9S163 in the Amish families allow this interval to be excluded as the location of CHH. We observed strong allelic association between CHH and D9S163 in both Amish and Finnish families, confirming the likely location of the CHH gene very close to this marker. Haplotype analysis of D9S163 and D9S165 in the Amish families suggests that only one mutation accounts for most CHH cases among them, as was expected and as is the case in Finland. Our data do not support the previously suggested hypothesis of a reduced penetrance as an explanation for the deficiency of affected children in the Amish families. We conclude that CHH is a single disease entity in the Amish and Finnish families and that the CHH gene is very close to D9S163 in 9p21-p13.

Child↗

An autosomal genomic screen for dementia in an extended Amish family.

Apolipoprotein E (APOE) is the only universally confirmed susceptibility gene for late-onset Alzheimer disease (LOAD), although many loci are believed to modulate LOAD risk. The genetic homogeneity of isolated populations, such as the Amish, potentially provide increased power to identify LOAD susceptibility genes. Population homogeneity in these special populations may reduce the total number of susceptibility genes contributing to the complex disorder, thereby increasing the ability to identify any one susceptibility gene. Dementia in the Amish is clinically indistinguishable from LOAD in the general population. Previous studies in the Amish demonstrated a significantly decreased frequency of the APOE-4 susceptibility allele, but significant familial clustering of dementia [M.A. Pericak-Vance, C.C. Johnson, J.B. Rimmler, A.M. Saunders, L.C. Robinson, E.G. D'Hondt, C.E. Jackson, J.L. Haines, Alzheimer's disease and apolipoprotein E-4 allele in an Amish population, Ann. Neurol. 39 (1996) 700-704]. These data suggested that a genetic etiology independent of APOE may underlie the dementia observed in this population. In the present analysis, we focused on a large, multiplex, inbred Amish family (24 sampled individuals; 10 of whom are affected). We completed a genomic screen to identify novel LOAD loci (n=316 genetic markers), using both model-dependent "affecteds-only" analysis (dominant and recessive) and model-independent affected relative pair analysis. Interesting results (lod>1.5 or p<0.01) were obtained for markers on eight chromosomes (2q, 5q, 6q, 7p, 8p, 8q, 11p, 18p, 18q, and 19q). The highest overall score was a multipoint lod score of 3.1 on chromosome 11p. Most regions we identified were not previously detected by genomic screens of outbred populations and may represent population-specific susceptibilities to LOAD. These loci are currently under further investigation in a study of LOAD including additional Amish families.

Alzheimer Disease↗

Cognitive impairment in the Amish: a four county survey.

BACKGROUND: The prevalence of probable dementia was determined in a rural, homogeneous community of Amish individuals in the Midwestern USA. The Amish are a genetically isolated group with a low level of formal education (< or = 8 years) and few exposures to modern life, who live in intergenerational setting and have strong social support networks. METHODS: Using community directories, trained interviewers administered the Mini Mental State Examination (MMSE) and a medical history survey to all Amish over 64 years old in a four county area. Individuals with scores < 27 (out of a maximum of 30 points) were given additional neuropsychological tests. Results were reviewed by a neuropsychologist and subjects were classified with regard to probable cognitive impairment. RESULTS: The MMSE scores were inversely related with age and directly with education. The Amish have higher MMSE scores than reported for the general US population. The overall prevalence of probable cognitive impairment for those over 64 years was 6.4%. The prevalence increased with age and lower education and was lowest among married individuals. CONCLUSIONS: The MMSE scores among the Amish were higher than the general population despite their low level of formal education. The lower level of cognitive impairment among the Amish could reflect a lack of inherited susceptibility to dementing diseases, or environmental factors characteristic of their traditional lifestyle. Even among this population with < or = 8 years of formal education, education may protect against cognitive impairment.

Age Distribution↗

Perinatal, infant, and child death rates among the Old Order Amish.

The Old Order Amish are a distinct ethnic group with a very high birth rate and patterns of perinatal risk factors quite different from those of the general population. This study reports marital fertility and perinatal, infant, and child death rates for an entire Amish settlement of approximately 10,000 individuals, centered around Geauga County, Ohio. All 6,623 births from 1948 to 1988 listed in a directory of Geauga Settlement Amish households were studied. The childbearing experience of all 475 married women over the age of 44 years was also described. Women aged > 44 years had a median of 8.3 births; 24% of the births were to women aged > 34 years. Despite a higher prevalence of several risk factors for perinatal and infant death among the Amish, neonatal and infant death rates for Geauga Settlement Amish have been very similar to the corresponding rates for white children in rural Ohio and the state as a whole. The beneficial aspects of Amish society that may lessen the impact of perinatal risk factors on mortality merit further study.

Adolescent↗

Vaccination usage among an old-order Amish community in Illinois.

The Old-Order Amish have low rates of vaccination and are at increased risk for vaccine-preventable diseases. A written survey was mailed to all Amish households in the largest Amish community in Illinois inquiring about their vaccination status and that of their children. In this survey, the Amish do not universally reject vaccines, adequate vaccination coverage in Amish communities can be achieved, and Amish objections to vaccines might not be for religious reasons.

Adolescent↗

Vesicle-associated membrane protein 4, a positional candidate gene on 1q24-q25, is not associated with type 2 diabetes in the Old Order Amish.

OBJECTIVE: The vesicle-associated membrane protein-4 (VAMP4) gene is an excellent type 2 diabetes (T2DM) positional candidate gene. It is located on chromosome 1q24-q25, a region of linkage to T2DM in the Amish and several other populations. VAMP4 is expressed in liver and skeletal muscle and participates in intracellular trafficking of secreted and membrane-associated proteins. DESIGN AND METHODS: We sequenced VAMP4 in 20 Amish subjects. Polymorphisms in and around VAMP4 were genotyped in 65 Amish subjects with T2DM, 64 subjects with impaired glucose homeostasis (IGH), and 126 normal glucose tolerant controls, as well as in an expanded set of 749 participants of the Amish Family Diabetes Study for whom glucose and insulin levels during an oral glucose tolerance test (OGTT) and other quantitative traits related to diabetes were available. Case-control and quantitative trait association analyses were performed. RESULTS: We found three common non-coding intragenic polymorphisms: a 23bp insertion/deletion (I/D) in the 5' untranslated region (UTR) in exon 1 at position 73127, and G35319T and C335296T single nucleotide polymorphisms (SNPs) in the 3' UTR (NCBI Accession No. Z98751). The two 3' UTR SNPs were in complete linkage disequilibrium (LD) and both were in strong LD with the exon 1 I/D polymorphism (|D'|=0.82). Similarly, three extragenic flanking SNPs (rs978985, rs203255, and rs1023479) showed moderate LD with the neighboring intragenic SNPs (|D'|=0.23-0.69). None of the SNPs individually nor any of the 2-, 3-, 4-, or 5-polymorphism haplotypes were associated with T2DM or IGH. The exon 1 I/D polymorphism was not associated with significant differences in mean fasting or stimulated glucose or insulin levels during an OGTT or other diabetes-related quantitative traits in the expanded set of 749 subjects. CONCLUSION: Variation in VAMP4 does not significantly influence risk of T2DM or IGH in the Amish.

Adaptor Proteins, Vesicular Transport↗

Rubella among the Amish: resurgent disease in a highly susceptible community.

Although the Amish make up less than 0.05% of the United States population, nearly all rubella reported in the United States in 1991 occurred in this population. In early 1991 a large rubella outbreak in a Tennessee Amish community that had experienced no rubella for 17 years afforded an opportunity to describe the epidemiology of rubella in this unique population. Structured interviews were conducted with 54 Amish families. Of 383 persons in the sample 85 (22%) had rubella. Illnesses were mild; 16% of cases lacked fever and 20% of cases reported no symptoms except rash. Children < 17 years of age were 7 times more likely than older individuals to be affected (77 of 214 vs. 8 of 165). All pregnant women in the community were > 20 years of age; none developed rubella. No congenital rubella syndrome was recognized. Although rubella is increasingly a disease of adolescents and young adults, in this outbreak, rubella was again a childhood disease. Illness in this community-based investigation was mild; rubella may be difficult to diagnose and report. Immunity after remote natural infection was durable since the community's last outbreak. Pregnant women probably were protected by the age distribution of immunity; this age distribution may not occur in other Amish populations. If preventable morbidity from rubella and other vaccine preventable diseases is to be avoided in this group, increased attention should be directed to encouraging vaccinations among Amish persons.

Disease Outbreaks↗

Periodontal disease in an Amish population.

Epidemiological studies of periodontal disease have attempted to focus on defined groups in which the variables thought to be responsible for disease could be controlled or more easily identified. This study documents periodontal disease parameters in a unique population of Amish farmers. A total of 371 Amish were contacted and 282 were examined in their homes giving a participation rate of 76%. Ages ranged from 18 to 79 years. Overall means for periodontal conditions were 1.54 mm for attachment loss, 2.63 mm for pocket depth, 0.17 for calculus, 0.63 for plaque and 0.61 for gingivitis. One dental examiner conducted all examinations. Prevalence of periodontal disease tended to be higher among males and increased with age. The majority of Amish examined had little evidence of destructive periodontal disease; about 3.4% of teeth examined had attachment loss of 6 mm or more. These findings indicate a modest level of periodontal disease among the Amish. It is of interest that this population does not generally seek routine dental care. Preliminary analyses of health behavior data collected indicate a lack of regular oral hygiene practices. It appears that the Amish may have protective factors which affect their level of disease.

Adolescent↗

Boundary maintenance as a barrier to mental health help-seeking for depression among the Old Order Amish.

This paper describes "boundary maintenance" as a barrier to help-seeking for depression within an Old Order Amish enclave. Observations and qualitative interview data were collected from 50 members of the Old Order Amish enclave and from the 8 mental health providers in their rural community. The Amish reported fairly high levels of depression, concomitantly high levels of reluctance to seek treatment for depression from mental health providers, and very low levels of service utilization. The functionality of boundary maintenance to group cohesion was discovered to be a significant barrier to help-seeking for depression from outside providers. Boundary maintenance was achieved through two social control mechanisms: religious-based stigmatization of depression and the construction of mental health providers as illegitimate help agents. Suggestions have been made to assist providers in achieving cultural competence among the Amish, in order to reduce the threat that the Amish perceive to their cultural boundaries.

Adult↗

A look into the Amish culture: what should we learn?

It is important to understand the Amish culture in order to provide appropriate, acceptable, and accessible health care to this culturally diverse group. A case study pertaining to the care of a dying elderly Amish woman living in a rural Amish community is examined. This allows for exploration into the world of the Amish community in greater detail. Their overall beliefs, values, and behavior are discussed as well as how their lifestyle affects their health care decisions, access to health care, and reimbursement of services. Nurse practitioners can offer culturally sensitive and appropriate health care to the Amish population by recognizing important cultural values that have survived for more than three hundred years.

Aged↗

Pertussis outbreak in an Amish community--Kent County, Delaware, September 2004-February 2005.

Vaccine-preventable disease outbreaks continue to occur among undervaccinated populations in the United States, including contained religious communities. The Amish practice separation from the world through group solidarity and caring for their own. Amish religious doctrine does not prohibit vaccination; however, coverage levels for routine childhood vaccination remain low in many Amish communities. This report describes an outbreak of pertussis in an Amish community in Kent County, Delaware, during September 2004-February 2005, that resulted in 345 cases and affected primarily preschool-aged children. The outbreak underscores the need to promote vaccination in Amish communities through culturally appropriate strategies, such as education and outreach to community leaders.

Adolescent↗

Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish.

Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity.

Bipolar Disorder↗

Cohen syndrome in the Ohio Amish.

We describe eight members from two large Amish kindreds who share a phenotype characterized by early-onset pigmentary retinopathy and myopia, global developmental delay and mental retardation, microcephaly, short stature, hypotonia, joint hyperextensibility, small hands and feet, common facial appearance, and friendly disposition. Several of the children had intermittent granulocytopenia. The phenotypic occurrence in three siblings coupled with the increased coefficient of inbreeding in the Amish suggested that this disorder is autosomal recessive and due to a single founder allele. Despite similarity to the clinical features of Cohen syndrome, experienced dysmorphologists attending the 23rd David W. Smith Workshop suggested the facial gestalt of the Amish children was inconsistent with this diagnosis. We mapped the locus responsible for these individuals' phenotype to chromosome 8q22-q23, which contains the recently discovered Cohen syndrome gene, COH1. Complete sequencing of the COH1 gene identified a likely disease-causing frameshift mutation and a missense mutation in the Amish patients. A comparison of features among different Cohen syndrome populations with shared linkage to the COH1 locus or known COH1 gene mutations may allow for the determination of improved clinical criteria on which to suspect the diagnosis of Cohen syndrome. We conclude that facial gestalt seems to be an unreliable indicator of Cohen syndrome between ethnic populations, although it is quite consistent among affected individuals within a particular ethnic group. Other features common to almost all individuals with proven COH1 mutations, such as retinal dystrophy, myopia, microcephaly, mental retardation, global developmental delay, hypotonia, and joint hyperextensibility appear to be better clinical indicators of this disorder.

Abnormalities, Multiple↗

The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases.

Cartilage-hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia, was originally described in the Old Order Amish in the United States and subsequently found to be unusually frequent among Finns. The major mutation causing CHH in Finns is a 70A --> G nucleotide substitution in the RMRP gene, which encodes the untranslated RNA that is a component of mitochondrial RNA-processing endoribonuclease. Here we report that the same mutation is the most frequent one, perhaps the only one, in the Amish population in which CHH was first characterized. The fact that the mutation segregates with the same major haplotype in these two populations and others suggests that it is very ancient. Unlike some other ordinarily rare recessive disorders that are limited in their high frequency to a single Amish deme (subisolate), e.g., Ellis-van Creveld syndrome, CHH occurs in high frequency in at least three distinct Amish demes, indicating, along with genealogic data, that there were multiple heterozygotes among the founders, as proposed by McKusick et al. [1965: Bull Johns Hopkins Hosp 116:231-272].

Endoribonucleases↗

Maternal lineages and Alzheimer disease risk in the Old Order Amish.

Old Order Amish, founded by a small number of Swiss immigrants, exist in culturally isolated communities across rural North America. The consequences of genetic isolation and inbreeding within this group are evident by increased frequencies of many monogenic diseases and several complex disorders. Conversely, the prevalence of Alzheimer disease (AD), the most common form of dementia, is lower in the Amish than in the general American population. Since mitochondrial dysfunction has been proposed as an underlying cause of AD and a specific haplogroup was found to affect AD susceptibility in Caucasians, we investigated whether inherited mitochondrial haplogroups affect risk of developing AD dementia in Ohio and Indiana Amish communities. Ninety-five independent matrilines were observed across six large pedigrees and three small pedigrees then classified into seven major European haplogroups. Haplogroup T is the most frequent haplogroup represented overall in these maternal lines (35.4%) while observed in only 10.6% in outbred American and European populations. Furthermore, haplogroups J and K are less frequent (1.0%) than in the outbred data set (9.4-11.2%). Affected case matrilines and unaffected control lines were chosen from pedigrees to test whether specific haplogroups and their defining SNPs confer risk of AD. We did not observe frequency differences between AD cases compared to controls overall or when stratified by sex. Therefore, we suggest that the genetic effect responsible for AD dementia in the affected Amish pedigrees is unlikely to be of mitochondrial origin and may be caused by nuclear genetic factors.

Alzheimer Disease↗