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Background Complementary and alternative medicine (CAM) in the form of vitamin and supplement use is increasingly prevalent in the United States. The interplay between CAM use and use of conventional medications is not well studied. We examined this issue in Old Order Amish (OOA), a population lacking several factors known to influence supplement use, whose culture and barriers to conventional medications may result in high rates of supplement use. Objective We characterized the patterns of supplement use in OOA, including the extent to which CAM use aggregates in families, and assessed whether higher use of supplements is associated with lower medication use. Design We conducted a cross-sectional study of conventional medications and supplements in 2,372 adult Amish from the Lancaster County, PA, area. Data were collected through face-to-face interviews. Supplements were subcategorized as herbal vs vitamin/mineral supplements. Results Seventy-seven percent of all Amish adults reported current supplement use, whereas 22% reported medication use. Women used supplements more often and used more supplements than men, and familial aggregation of supplement use was stronger in family pairs involving women. Supplement use was associated with less medication use after controlling for age, sex, body mass index, and self-reported histories of hypertension, diabetes, and hyperlipidemia (adjusted odds ratio [OR] 0.96, 95% CI 0.92 to 1.00; P =0.047). This association was driven primarily by use of herbal supplements (adjusted OR 0.94, 95% CI 0.89 to 0.99; P =0.025) as vitamin/mineral supplements were not associated with different use of medication (adjusted OR 0.99, 95% CI 0.90 to 1.09; P =0.8). In analyses limited to cardiovascular medications and cardiovascular supplements in participants with hyperlipidemia, hypertension, or diabetes, supplement use was not associated with conventional medication use. Conclusions OAA, particularly women, take dietary supplements much more frequently than they use conventional medications. Use of herbal supplements is associated with less use of conventional medications, whereas vitamin/mineral supplement use is not. [ABSTRACT FROM AUTHOR]

Background: The burden of diabetes and cardiovascular risk is not uniform across the USA, with much of this disparity tracking differences in socioeconomic status, cultural practices and lifestyle. To further evaluate disparities in these disorders, we assessed the prevalence of diabetes, hypertension, and hypercholesterolemia in an Old Order Amish community that is characterized by distinctive sociocultural practices that include a very cohesive social structure and limited use of modern technologies and medications. We compared prevalence of these conditions with that of the overall US population., Method: We performed a community-wide survey in 5377 Amish individuals aged 18 years and older from the Lancaster County, Pennsylvania, Amish settlement that included a basic physical examination and fasting blood draw during the period 2010-2018. We then compared the prevalence of diabetes, hypertension, and high cholesterol, defined using standard criteria, between the Amish and the European Caucasian subsample of the 2013-2014 US National Health and Nutrition Examination Survey (NHANES)., Results: Prevalence rates for diabetes, hypertension and hypercholesterolemia were 3.3%, 12.7%, and 26.2% in the Amish compared with 13.2%, 37.8% and 35.7% in NHANES (p<0.001 for all). Among individuals with these disorders, Amish were less likely to be aware that they were affected, and among those aware, were less likely to be treated with a medication for their disorder., Conclusion: There is substantially lower prevalence of diabetes, hypertension and hypercholesterolemia in the Amish compared with non-Amish Caucasians in the USA. Possible factors contributing to this disparity include higher physical activity levels in the Amish or other protective sociocultural factors, a greater understanding of which could inform risk reduction interventions for these chronic diseases., Competing Interests: Competing interests: ARS is an employee of Regeneron Pharmaceuticals, Inc and receives compensation., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Previous research has suggested that the Amish may experience a relatively high prevalence of Parkinson's disease (PD) and/or parkinsonian motor signs., Methods: In a large sample from the Amish community in Lancaster County, Pennsylvania, age ≥18 years, we assessed the prevalence of self-reported PD diagnosis. For those without self-reported PD diagnosis, we assessed the frequency of PD-related motor symptoms using a 9-item questionnaire that was designed by the PD Epidemiology Research Group. Lastly, we queried study participants for the presence of 2 nonmotor symptoms that have been commonly linked to PD: bowel movement frequency and daytime sleepiness., Results: Among 2,025 subjects who answered the PD questionnaire, 430 were older than 60 years. Of 430 participants ≥60 years, 5 (1.2%) reported a PD diagnosis. Of those without a PD diagnosis, 10.5% reported ≥1 and 1.2% ≥ 4 motor symptoms for the 9-item PD screening questionnaire. Of the 3,789 subjects who answered the question about bowel movement frequency, 0.7% reported ≤3 bowel movements per week. Among 1,710 subjects who answered the question about daytime sleepiness, 8.1% of the participants reported "always" sleepy during the day., Discussion: These data neither support a markedly higher PD prevalence in the older Lancaster Amish nor do they show dramatically higher motor and/or selected nonmotor symptoms than the general population. Future studies that employ more rigorous procedures for case identification and PD-specific preclinical symptoms/tests are needed to determine the potential differences and similarities among different Amish populations and between Amish and non-Amish populations., (© 2020 S. Karger AG, Basel.)

Study Objectives: We hypothesized that sleep duration in the Amish would be longer than in non-Amish., Methods: Sleep duration was obtained by questionnaire administered to Amish individuals (n = 3,418) and from the 2015-2016 National Health and Nutrition Examination Survey (NHANES; n = 1,912). Self-reported sleep duration was calculated as the difference in usual times that the participants went to bed at night and woke up in the morning., Results: In Amish (43.7 ± 16.7 years) and NHANES (50.0 ± 20.6 years), women had a longer sleep duration than men (P < .0001 in both groups) and sleep was significantly longer in those aged 18-29 years and ≥ 70 years, compared to those aged 30-69 years. Seasonal-adjusted sleep duration was shorter in Amish than that in NHANES (7.8 minutes shorter, age- and sex-adjusted P < .0001). However, Amish were less likely to report sleeping fewer than 7 hours per night (15.4% in Amish versus 20.5% in NHANES, P < .0001). Amish went to bed 80.4 minutes earlier than NHANES and arose 87.6 minutes earlier (age-, sex-, and season-adjusted P < .0001 for both). In the Amish, sleep duration was longer in clerks than in farmers (P < .0001) and was significantly correlated among household members (.15 < r < .62, P < .001), although there was no evidence that this trait was heritable (h² approximately 0) after adjustment for household., Conclusions: The lower frequency of short sleepers in the Amish may contribute to the relatively lower risks of cardiometabolic diseases observed in this population., Citation: Zhang M, Ryan KA, Wickwire E, Postolache TT, Xu H, Daue M, Snitker S, Pollin TI, Shuldiner AR, Mitchell BD. Self-reported sleep duration and pattern in old order amish and non-amish adults. J Clin Sleep Med. 2019;15(9):1321-1328., (© 2019 American Academy of Sleep Medicine.)

Background: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels., Methods: To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for coronary artery calcification (CAC) in 1018 of these individuals., Results: From the initial genome-wide association study, a cluster of single nucleotide polymorphisms in the region of the apolipoprotein B-100 gene (APOB) was strongly associated with LDL-C levels (P < 10(-68)). Additional genotyping revealed the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, which was also strongly associated with LDL-C in the replication sample (P < 10(-36)). The R3500Q carrier frequency, previously reported to be 0.1% to 0.4% in white European individuals, was 12% in the combined sample of 1504 Amish participants, consistent with a founder effect. The mutation was also strongly associated with CAC in both samples (P < 10(-6) in both) and accounted for 26% and 7% of the variation in LDL-C levels and CAC, respectively. Compared with noncarriers, R3500Q carriers on average had LDL-C levels 58 mg/dL higher, a 4.41-fold higher odds (95% confidence interval, 2.69-7.21) of having detectable CAC, and a 9.28-fold higher odds (2.93-29.35) of having extensive CAC (CAC score ≥400)., Conclusion: The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.

Background: Because they are a closed founder population, the Old Order Amish (OOA) of Lancaster County have been the subject of many medical genetics studies. We constructed four versions of Anabaptist Genealogy Database (AGDB) using three sources of genealogies and multiple updates. In addition, we developed PedHunter, a suite of query software that can solve pedigree-related problems automatically and systematically., Methods: We report on how we have used new features in PedHunter to quantify the number and expected genetic contribution of founders to the OOA. The queries and utility of PedHunter programs are illustrated by examples using AGDB in this paper. For example, we calculated the number of founders expected to be contributing genetic material to the present-day living OOA and estimated the mean relative founder representation for each founder. New features in PedHunter also include pedigree trimming and pedigree renumbering, which should prove useful for studying large pedigrees., Results: With PedHunter version 2.0 querying AGDB version 4.0, we identified 34,160 presumed living OOA individuals and connected them into a 14-generation pedigree descending from 554 founders (332 females and 222 males) after trimming. From the analysis of cumulative mean relative founder representation, 128 founders (78 females and 50 males) accounted for over 95% of the mean relative founder contribution among living OOA descendants., Discussion/conclusions: The OOA are a closed founder population in which a modest number of founders account for the genetic variation present in the current OOA population. Improvements to the PedHunter software will be useful in future studies of both the OOA and other populations with large and computerized genealogies.

Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.

Transcription factor 7-like 2 (TCF7L2) regulates genes involved in cell proliferation and differentiation. The TCF7L2 gene is located on chromosome 10q25 in a region of replicated linkage to type 2 diabetes. Recently, a microsatellite marker in intron 3 (DG10S478) and five correlated single nucleotide polymorphisms (SNPs) were identified in Icelandic individuals that showed strong association with type 2 diabetes, which was replicated in Danish and European-American cohorts. We genotyped four of the SNPs (rs7901695, rs7903146, rs11196205, and rs12255372) in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT; n = 139), and normal glucose tolerance (NGT; n = 342). We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008-0.01; OR 1.53-1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively). In an expanded set of 698 Amish subjects without diabetes, we found no association with insulin and glucose levels during a 3-h oral glucose tolerance test. We also genotyped these SNPs in nondiabetic, non-Amish subjects (n = 48), in whom intravenous glucose tolerance tests were performed, and found an association between rs7901695 and rs7903146 and insulin sensitivity (P = 0.003 and P = 0.005, respectively) and disposition index (P = 0.04 and P = 0.007, respectively). These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity.

Background: The relationship between parity and life span is uncertain, with evidence of both positive and negative relationships being reported previously. We evaluated this issue by using genealogical data from an Old Order Amish community in Lancaster, Pennsylvania, a population characterized by large nuclear families, homogeneous lifestyle, and extensive genealogical records., Methods: The analysis was restricted to the set of 2,015 individuals who had children, were born between 1749 and 1912, and survived until at least age 50 years. Pedigree structures and birth and death dates were extracted from Amish genealogies, and the relationship between parity and longevity was examined using a variance component framework., Results: Life span of fathers increased in linear fashion with increasing number of children (0.23 years per additional child; p =.01), while life span of mothers increased linearly up to 14 children (0.32 years per additional child; p =.004) but decreased with each additional child beyond 14 (p =.0004). Among women, but not men, a later age at last birth was associated with longer life span (p =.001). Adjusting for age at last birth obliterated the correlation between maternal life span and number of children, except among mothers with ultrahigh (>14 children) parity., Conclusions: We conclude that high parity among men and later menopause among women may be markers for increased life span. Understanding the biological and/or social factors mediating these relationships may provide insights into mechanisms underlying successful aging.

Lifespan is a complex phenotype determined by the interaction of genetic and environmental factors. This makes the identification of variants in genes that influence longevity challenging. We believe that the Old Order Amish (OOA) of Lancaster, Pennsylvania is an excellent population for studying the genetics of longevity. They are a closed population derived from a limited number of founders. They have large families and maintain extensive genealogic records dating to the 1700 s. They eschew modern technology; their lifestyle is little changed over the last 250 years. Homogeneity of environment and lifestyle factors across time and across the OOA population minimizes the influence that environmental factors have in determining the differences in lifespan between individuals. We hypothesize that this reduction in environmental variability will make it easier to identify the genetic factors that influence lifespan. In this article, we describe our strategy for identifying variants in genes that influence longevity in the Amish and present the results of our studies to date.

Objective: Metabolic syndrome is associated with increased risk for cardiovascular disease and type 2 diabetes mellitus (T2DM). The lamin A/C (LMNA) gene, mutations of which cause rare syndromes of severe insulin resistance and dyslipidemia, is located on chromosome 1q21-q24, a region linked to T2DM in several genome wide scans, including in the Old Order Amish. To determine whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and its constituent components., Methods and Results: We performed DNA sequence analysis of LMNA. Six single-nucleotide polymorphisms (SNPs) were identified: c.141889C>T (intron 3), c.141906G>T (intron 3), A287A (c.141253T>C; exon 5), c.140353G>A (intron 6), c.139418C>T (intron 8), and H566H (c. 138747C>T; exon 10). In 971 participants from the Amish Family Diabetes Study, the H566H polymorphism of LMNA was associated with metabolic syndrome diagnosed according to National Cholesterol Education Program ATP III criteria and also higher mean fasting triglyceride and lower mean high-density lipoprotein-cholesterol concentrations. However, no differences in allele frequencies were observed for any SNP among participants with T2DM or impaired glucose homeostasis (IGH) and normoglycemic controls. Haplotype analysis showed that >87% of individuals carried 1 of 2 common LMNA haplotypes. There were no significant differences in haplotype frequencies among subjects with metabolic syndrome T2DM, IGH, and controls., Conclusions: Sequence variation in LMNA may confer modest susceptibility for development of metabolic syndrome and dyslipidemia in the Amish. To determine whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and its constituent components, we performed DNA analysis of polymorphisms in LMNA. The H566H polymorphism was associated with metabolic syndrome and also higher mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the Old Order Amish.

Unlabelled: The incidence of hip fracture was estimated in a community of Old Order Amish and compared with available data from non-Amish whites. Hip fracture rates were 40% lower in the Amish, and the Amish also experienced higher BMD., Introduction: Understanding the patterns of fracture risk across populations could reveal insights about bone health and lead to the earlier detection and prevention of osteoporosis. Toward this aim, we compared hip fracture incidence and bone mineral density (BMD) between an Old Order Amish (OOA) community, characterized by a rural and relatively active lifestyle, and non-Amish U.S. whites., Materials and Methods: All hospital admissions for hip fracture among OOA individuals in Lancaster County, PA, were identified between 1995 and 1998 from four area hospitals. Hip fracture incidence was calculated by cross-referencing an available Anabaptist genealogy database with communities located within these hospital service areas and compared with non-Amish whites obtained from National Hospital Discharge data. Additionally, BMD at the hip was compared between 287 Amish subjects and non-Amish whites from the National Health and Nutrition Examination Survey III survey., Results and Conclusions: OOA experienced 42% fewer hip fractures than would be expected had they experienced the same rate of hip fracture as observed in non-Amish whites (p < 0.01) and a higher mean BMD that was significant in women (p < 0.05) but not men. Further evaluation of lifestyle and/or genetic differences between Amish and non-Amish populations may shed insights into etiologic factors influencing hip fracture risk.

Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P < 0.01) to autoimmune thyroiditis and/or AITD-hypothyroidism was also detected in five other regions. We conclude that a gene on chromosome 5q11.2-q14.3 is likely to contribute to susceptibility to AITD in the Amish.