Order Amish Research Articles

Amish Land Ownership within Wisconsin

ABSTRACT Rapid growth of Amish settlement within Wisconsin over the past 60 years has brought 200,000 acres of land under Amish ownership. This paper studies patterns of Amish landownership within 27 settlements, representing 71 percent of Wisconsin’s Amish church districts, and illustrates differing average land ownership per household and degrees of land dispersal and concentration among the settlements. Average household land ownership ranged from 27.7 to 86.6 acres among the studied Old Order Amish settlements. Most Amish owned lands are dispersed among lands that remain under “English” ownership. Older and larger settlements display greater concentrations of Amish owned lands, whether measured by maximum acreage per survey section within the settlement, average owned acreage per section, and presence or absence of non-contiguous sections of Amish owned lands. Amish church affiliation, origins of Amish within the settlements, and types of occupational engagement also appear related to these differences. Keywords: agriculture, Amish, landownership, Old Orders, Wisconsin

571. Fertility is Negatively Associated With the Global Seasonality Score in Old Order Amish Women

571. Fertility is Negatively Associated With the Global Seasonality Score in Old Order Amish Women

Psychometric approaches to defining cognitive phenotypes in the Old Order Amish.

Memory and cognitive problems are central to the diagnosis of Alzheimer's disease (AD). Psychometric approaches to defining phenotypes can aid in identify genetic variants associated with AD. However, these approaches have mostly been limited to affected individuals. Defining phenotypes of both affected and unaffected individuals may help identify genetic variants associated with both AD and healthy aging. This study compares psychometric methods for developing cognitive phenotypes that are more granular than clinical classifications. 682 older Old Order Amish individuals were included in the analysis. Adjusted Z-scores of cognitive tests were used to create four models including (1) global threshold scores or (2) memory threshold scores, and (3) global clusters and (4) memory clusters. An ordinal regression examined the coherence of the models with clinical classifications (cognitively impaired [CI], mildly impaired [MI], cognitively unimpaired), APOE-e4, sex, and age. An ANOVA examined the best model phenotypes for differences in clinical classification, APOE-e4, domain Z-scores (memory, language, executive function, and processing speed), sex, and age. The memory cluster identified four phenotypes and had the best fit (χ2 =491.66). Individuals in the worse performing phenotypes were more likely to be classified as CI or MI and to have APOE-e4. Additionally, all four phenotypes performed significantly differently from one another on the domains of memory, language, and executive functioning. Memory cluster stratification identified the cognitive phenotypes that best aligned with clinical classifications, APOE-e4, and cognitive performance We predict these phenotypes will prove useful in searching for protective genetic variants.

Associations of genome-wide and regional autozygosity with 96 complex traits in old order Amish

Background: Autozygosity, the proportion of the genome that is homozygous by descent, has been associated with variation in multiple health-related traits impacting evolutionary fitness. Autozygosity (FROH) is typically measured from runs of homozygosity (ROHs) that arise when identical-by-descent (IBD) haplotypes are inherited from each parent. Population isolates with a small set of common founders have elevated autozygosity relative to outbred populations. Methods: In this study, we examined whether degree of autozygosity was associated with variation in 96 cardiometabolic traits among 7221 Old Order Amish individuals residing in Lancaster County, PA. We estimated the average length of an ROH segment to be 6350 KB, with each individual having on average 17.2 segments 1.5 KB or larger. Measurements of genome-wide and regional FROH were used as the primary predictors of trait variation in association analysis. Results: In genome-wide FROH analysis, we did not identify any associations that withstood Bonferroni-correction (p = 0.0005). However, on regional FROH analysis, we identified associations exceeding genome-wide thresholds for two traits: serum bilirubin levels, which were significantly associated with a region on chromosome 2 localized to a region surrounding UGT1A10 (p = 1 × 10− 43), and HbA1c levels, which were significantly associated with a region on chromosome 8 localized near CHRNB3 (p = 8 × 10− 10). Conclusions: These analyses highlight the potential value of autozygosity mapping in founder populations.

Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population.

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. Our findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies.

The Work of Pioneering Amish Studies Scholar Walter Kollmorgen: Annontations of His 1940s Amish Publications

Walter Kollmorgen’s two seminal contributions to Amish studies scholarship include the 1942 report “Culture of a Contemporary Rural Community: The Old Order Amish of Lancaster County, Pennsylvania” published by the U.S. Department of Agriculture’s Bureau of Agricultural Economics, and his 1943 article “The Agricultural Stability of the Old Order Amish and Old Order Mennonites of Lancaster County, Pennsylvania” published in the American Journal of Sociology. His 1942 report was one of six mixed-methods studies that analyzed the relative in/stability of rural American communities during the Great Depression. The six-part series concluded that the Amish of Lancaster County, PA, weathered the Great Depression with fortitude. In Kollmorgen’s subsequent 1943 AJS article, he consolidated key findings from field research, summarizing why the Old Order Amish and Old Order Mennonite people persist as a distinctive sect. Representing the very first substantial Amish studies scholarship (alongside Bachman’s 1942 The Old Order Amish of Lancaster County), Kollmorgen’s work merits ongoing re-examination, as it defined the conversation and trajectory of Amish studies scholarship. In this essay, I annotate both works, distilling his findings into summary essays that focus on presenting his research as a resource for readers and not necessarily engaging with it. Given the diffuseness of his report’s data, I provide both short summaries of each chapter and full chapter annotations. [Abstract by author.]

The 1955 Diener Beschluss: Text, Interpretation, Reception History, and Historiography

The contemporary diversity of the Amish is well attested by recent literature in the field of Amish studies. However, beyond Leroy Beachy’s Unser Leit, insufficient attention has been given to the question of how this state of affairs came about. The most consequential date in the twentieth century is September 1955, when a Bescluß (statement) that was issued at a churchwide ministers’ meeting ultimately divided the Old Order Amish into two separate, non-communing fellowships. Three important historical details about the meeting merit consideration: the document issued on the last day of the churchwide ministers’ meeting circulates among the Amish in three different forms; the document itself was interpreted differently by attendees; and some of the attendees skipped the final day of the meeting when the official statement was presented by the seven-member bishop committee. After subjecting the extant forms of the ministerial decision to textual analysis, this essay interprets the meaning of the document in light of previous ministerial statements (issued in 1809, 1865, 1913, 1917, 1941, 1946, and 1953) and through its reception history among the Amish down to the present day, to sharpen the historiography of the Amish in North America in the twentieth century. [Abstract by author.]

Health Beliefs, Health Practices, and Health-Seeking Behaviors among Swartzentruber Amish in Clark County, Wisconsin

Although the literature contains valuable information about Amish culture, few qualitative studies have been conducted on the health beliefs, health practices, and health-seeking behaviors of the Swartzentruber Amish, the most conservative group of Old Order Amish. The purpose of this study was to describe these dynamics for the Swartzentruber Amish of Clark County, Wisconsin. Utilizing the grounded theory approach, 25 participants were interviewed and seven themes were identified: shared decision-making is common in families; causes of illness are believed to be etiological or the will of God; home remedies are the first choice; preventive medicine is an unfamiliar concept; health information is sought from within their settlement; and professional medical care is a last resort in treatment. These Amish identified several obstacles to seeking or using professional medical care: unfamiliarity with the English medical system; communication barriers; lack of trust in medical professionals; the high cost of medical care; belief of diminished or no say in a child’s healthcare; and concern about prescription drugs. An understanding of the Swartzentruber Amish is important if healthcare professionals are to provide them with culturally congruent care. Numerous recommendations based on the findings are included for healthcare providers. [Abstract by author.]

Assessing the Attitudes and Perceptions of the Old Order Amish toward Genetic Testing for Familial Defective Apolipoprotein B-100

Through a founder effect, one in eight Lancaster County, PA, Amish harbors the pathogenic APOB variant R3527Q, causing Familial Defective Apolipoprotein B-100 (FDB) that is rare in the general population. Affected individuals are at increased risk for high low density lipoprotein (LDL) cholesterol levels and cardiovascular disease and may benefit from early screening and treatment. A qualitative interview approach was used to investigate the genetic risk perceptions of the Amish and their attitudes towards genetic testing for FDB. The goal was to identify elements necessary for a successful program that would identify high risk individuals in the Lancaster County Amish community and provide them with potentially lifesaving education and interventions. Thirty interviews were conducted. Collected data were analyzed and coded for common themes. Participants perceived a great deal of importance in genetic risk and were aware of the significant impact genetics have on health. Most individuals perceived genetic risk as more significant than family history. Twenty-four of 30 individuals would consider testing; of these, all 24 reported they would take proactive measures to reduce risks if given a positive result. Most would prefer diet modification and natural health remedies, with prescription medication only as a last resort. Several participants stated that most Amish people would be unlikely to test if they were feeling healthy. Cost was the most significant barrier to pursuing testing. Implementing a successful screening program would require community outreach and awareness, risk reduction education and support, and minimal out-of-pocket expenses. The program’s success provides insights into the efficacy of predictive genetic screening for the general population. [Abstract by authors.]

Subjectivity in the Lancaster Amish Community Study of 1940-42: 'Economic Conquest' in Loomis’s Diary and Rosinow’s Photographs

The American Farm Community Study (1940), funded by the USDA’s Bureau of Agricultural Economics, was a social investigation that sought to determine why some rural communities thrive while others fail. To conduct the Study, the Bureau sent social scientists to six rural communities across the country to investigate and document the most and least “stable” American communities. Geographer Walter Kollmorgen, sociologist Charles Loomis, and photographer Irving Rusinow documented the Old Order Amish of Lancaster County, PA, as the “most stable” community in the Study. In Lancaster, the men found a people thriving in the midst of english neighbors still economically reeling from depression and war. In existing research, Kollmorgen’s neutral/distant data collection effort receives the most attention. This study focuses on the subjectivity of Charles Loomis’ and Irving Rustow’s data collection. Loomis collected data in a personal-style diary while working as a farmhand on a former english farm taken over by an Amishman. Rusinow photographed landscapes that visually portrayed how Amish took over dilapidated english farmsteads, suggesting Amish community stability went hand-in-hand with economic conquest. Together, in word and image, Loomis and Rusinow described the Amish via narratives of conquest, empire, nascent Nationalism, and (re)valuations of the (Anglo) American dream. [Abstract by author.]

Plasma pTau181 is associated with impaired cognition in the Old Order Amish and adds additional information beyond the known genetic risk factors for AD

AbstractBackgroundAs plasma biomarker assays have become more widely available, they are increasingly being used to characterize AD and related dementias. The Old Order Amish are a cultural and genetic isolate in the US that have participated in genetic studies for decades. This study investigated plasma phosphorylated tau at threonine‐181 (pTau181) in an Old Order Amish cohort to determine if the association with cognitive status is reproducible in this population.MethodOld Order Amish individuals over age 65 (n=467, mean age = 81.3, 60.6% female) in Indiana and Ohio were examined using a modified Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery. Each individual was assigned Impaired (n=155, mean age = 82.5, 56.8% female) or Unimpaired (n=312, mean age = 80.8, 62.5% female) cognitive status via consensus review of these examination results. The level of plasma pTau181 was measured using the pTau181 Advantage V2 assay from Quanterix. Genetic Risk Scores (GRS) were calculated using genome‐wide significant variants from Kunkle et al. (2019), weighted by log odds ratio estimates. A t‐test was used to compare plasma pTau181 levels between the Impaired and Unimpaired groups. Logistic regression was then used to model the contribution of age, sex, GRS, and plasma pTau181 on cognitive status.ResultWe found that the average level of plasma pTau181 was significantly higher in the Impaired group (2.46 pg/mL) compared to the Unimpaired group (2.01 pg/mL) at p<0.0001. A multivariable model found increasing age (OR=1.10, p=0.0002), male sex (OR=1.60, p=0.04), increasing GRS (OR=1.97, p<0.0001), and increasing plasma pTau181 (OR=1.46, p=0.001) associated with impaired cognitive status. The effect of GRS is mostly attributable to APOE.ConclusionThe result of these analyses indicates that pTau181 is associated with impaired cognitive status in the Old Order Amish, adding additional information beyond the known genetic risk factors for AD.

Amish Mortality Rates in the Twenty-First Century

This research documents the mortality rates of the Amish from 2014 through 2021 using data found in The Diary of the Old Order Churches, a monthly publication designed to serve the Old Order Amish throughout the Americas. Data collected included month and year of death, age at death, gender, place of death by state/province/country, reported cause of death, and family name of parents in cases of stillbirth or infant mortality. Data revealed that the Amish have experienced five peaks in death rates, two prior to COVID and three during the COVID pandemic. Data also revealed differences in deaths due to accidents, cancer, and heart issues related to gender.

The Varying Fertilities of the Amish Groups of Holmes County, Ohio

The Amish are known for their high fertility, and one of the groups, the Swartzentruber Amish, is known for its exceptionally large families. Opinions vary about the number, but there are many distinct Amish affiliations in the Holmes County, Ohio, area, ranging from the progressive New Order Amish to the ultraconservative Swartzentruber Amish. In this study, fertility was calculated for the five groups large enough for such analysis. The fertilities (i.e., number of live births for women 45 years and over) were notably congruent with the degree of conservatism (from progressive to conservative): New Order, 5.76; Old Order, 6.09; Dan or Andy Weaver, 7.79; Hostetler, 8.68; Swartzentruber, 10.42. The families of the Old Order group (the only group large enough) were subdivided into farming and nonfarming subgroups and families of ministers and families of laymen for fertility comparisons. The farming families subgroup had a higher fertility rate (6.88) than the nonfarming subgroup (5.90), presumably because their labor-intensive work of farming begs for large families. The ministers’ family subgroup also had a higher fertility (6.54) than the laymen’s family subgroup (5.89), the difference being attributed to ministers having a deeper religious commitment than laymen. The interval between marriage and first birth was nearly the same for all five groups. For the Swartzentruber Amish, the interbirth intervals remained short throughout the reproductive span, but for the other four groups, they became progressively longer. The reproductive span of women in the New Order Amish group was 13.75 years. It was progressively longer for the more conservative groups and was longest (17.74 years) for Swartzentruber Amish. These results are consistent with other studies that showed that people with more intense religious practice have larger families than people whose religious practice is less intense.

A Demographic Profile of the Elkhart-LaGrange Old Order Amish Settlement

In 1970, Johns Hopkins University produced the first Indiana Amish directory. Its goals were narrowly related to genetic research, and it opened a window into a nearly complete census of this settlement. It is rare in social science to have such a complete picture of any population. A decade later, the second directory was published. The Amish decided to put their own energy into producing this compendium of birth dates, family size, district maps, and detailed information on the ministerial history of the settlement. Using the data from eight directories, we can provide a nearly complete analysis of demographic change in the third largest Amish settlement in the world. In this study, we look at growth in settlement size, changes in family size, migration in and out of the settlement, defection and retention of Amish young people, the growth in nonfarm occupations over time, and the frequency of prominent family names.

ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction

Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities. While the role of ITCH protein in apoptosis and inflammation has previously been characterized, a defect in cellular bioenergetics has not yet been reported in ITCH deficiency. Here we present a Caucasian female originally evaluated for possible mitochondrial respiratory chain deficiency, who ultimately was found to have two novel variants in ITCH with absence of ITCH protein in patient derived fibroblasts. Clinical studies of patient muscle showed mitochondrial DNA copy number of 57% compared to controls. Functional studies in skin fibroblasts revealed decreased activity of mitochondrial fatty acid oxidation and oxidative phosphorylation, and decreased overall ATP production. Our findings confirm mitochondrial energy dysfunction in a patient with ITCH deficiency offering the opportunity to assess alternative therapeutic options.

The «Amish» NM_000256.3:c.3330+2T>G splice variant in MYBPC3 associated with hypertrophic cardiomyopathy is an ancient Swiss mutation

MYBPC3 is the most frequently mutated gene in hypertrophic cardiomyopathy (HCM). Several loss-of-function founder variants have been reported in MYBPC3 from various geographic regions, altogether suggestive of a modest or absent effect of these variants on reproductive fitness. One of them, a MYBPC3 splice variant, NM_000256.3:c.3330+2T > G, was first described in homozygous state in newborns presenting with a severe, recessive form of HCM among the Amish population and was later associated with adult-onset dominant HCM in heterozygous carriers. We here report this splice variant in heterozygous state in eight unrelated Swiss families with HCM, making it the most prevalent cardiomyopathy variant in western Switzerland. This variant was identified in patients using targeted (n = 5) or full-genome sequencing (n = 3). Given the prevalence of this variant in the Old Order Amish, Mennonites and Swiss populations, and given that both Amish and Mennonites founders originated from the Bern Canton in Switzerland, the MYBPC3, NM_000256.3:c.3330+2T > G variant appears to be of Swiss origin. Neighboring regions that hosted the first Amish settlements (Alsace, South Germany) should be on the lookout for that variant. The existence of MYBPC3 founder variants in different populations suggests that individuals with early-onset clinical disease may be the tip of the iceberg of a much larger number of asymptomatic carriers. Alternatively, reproductive fitness could even be slightly increased in some variant carriers to compensate for the reduction of fitness in the more severely affected ones, but this remains to be investigated.

Phenylalanine hydroxylase (PAH) deficiency in old order Amish communities: from genotype to clinical management.

Phenylalanine hydroxylase (PAH) deficiency in old order Amish communities: from genotype to clinical management.

Impact of parental relatedness on reproductive outcomes among the Old Order Amish of Lancaster County.

Genetically isolated populations that arise due to recent bottleneck events have reduced genetic variation reflecting the common set of founders. Increased genetic relatedness among members of isolated populations puts them at increased risk for some recessive disorders that are rare in outbred populations. To assess the burden on reproductive health, we compared frequencies of adverse reproductive outcomes between Amish couples who were both heterozygous carriers of a highly penetrant pathogenic or likely pathogenic variant and noncarrier couples from the same Amish community. In addition, we evaluated whether overall genetic relatedness of parents was associated with reproductive outcomes. Of the 1824 couples included in our study, 11.1% were at risk of producing a child with an autosomal recessive disorder. Carrier couples reported a lower number of miscarriages compared to noncarrier couples (p=0.02), although the number of stillbirths (p=0.3), live births (p=0.9), and number of pregnancies (p=0.9) did not differ significantly between groups. In contrast, higher overall relatedness between spouses was positively correlated with number of live births (p < 0.0001), pregnancies (p < 0.0001), and stillbirths (p=0.03), although not with the number of miscarriages (p=0.4). These results highlight a complex association between relatedness of parents and reproductive health outcomes in this community.

Twinning Characteristics of the Amish Groups of Holmes County, Ohio

The Amish are known for their high fertility and large families, but the Amish twinning rate has been of less interest. In an article published in 1970 (over 50 years ago), Cross and McKusick determined the Holmes County, Ohio, Amish twinning rate to be 15.3 twin pairs per 1,000 live births, which ranked among the highest known twinning rates at that time, while the U.S. national twinning rate hovered at around 9 per 1,000 per year. Within a few decades following the Cross and McKusick study, the twinning rates of the American population increased dramatically, and surpassed the Amish twinning rates. This surge in the twinning rate among the general American population was generally accredited to the widespread use of medically assisted reproduction (MAR), which favors multiple births, and the increased birth rates for older women, who have a significantly higher rate of multiple births. Holmes County has eight different Amish sects, ranging from fairly progressive to ultraconservative, and the five largest ones were the subjects of this study. The twinning rates of the different groups vary, parallel with degree of conservatism. The New Order Amish (most progressive) have a twinning rate of 20.1 twins per 1,000 births, whereas the Swartzentruber Amish have a rate of 34.5. Since all the groups are of identical ethnic stock and share virtually identical historical experiences, these twinning variances are difficult to explain, but may be due to diverging dietary practices that paralleled the conservative fragmentation.

EP085: Phenotype of two old order Amish patients with NOD2 increased risk alleles

Nucleotide-binding oligomerization domain containing 2 (NOD2) is a member of a family of intracellular proteins involved in various inflammatory processes. NOD2 sequence variants have been associated with Crohn’s disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID). Three main NOD2 variants (p.Arg702Trp, p.Gly908Arg and p.Leu1007Profs*2) (NM_022162.2) are linked not only to Crohn’s disease (CD) but also to NAID, which is a multisystem inflammatory disease. Dermatitis is a major feature of the NAID clinical phenotype and often presents as erythematous patches and plaques primarily occurring on the trunk.