Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study.

Objective: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups.

Methods: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA).

Genome-wide association analysis of metabolic syndrome quantitative traits in the GENNID multiethnic family study.

Background: To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups.

Methods: Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin.

Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families.

Background: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking.

APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease.

Importance: Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.

Objective: To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD.

Evaluation of mild cognitive impairment subtypes in Parkinson's disease.

Mild cognitive impairment in Parkinson's disease (PD-MCI) is common and increases the risk for dementia. Establishing distinct PD-MCI cognitive subtypes could be valuable for eventually predicting those most likely to convert to dementia. However, the study of PD-MCI subtypes has not yielded consistent results among cohorts.

Association mapping of the PARK10 region for Parkinson's disease susceptibility genes.

Background: Previous studies indicate that as many as six genes within the PARK10 region (RNF11, UQCRH, HIVEP3, EIF2B3, USP24, ELAVL4) might modify susceptibility or age at onset in Parkinson's disease (PD).

Methods: We sought to identify new PD susceptibility genes and to validate previously nominated candidate genes within the PARK10 region using a two-stage design. We used data from a large, publicly-available genome-wide association study (GWAS) in the discovery stage (n = 2000 cases and 1986 controls) and data from three independent studies for the replication stage (total n = 2113 cases and 2095 controls).

APOE ε4 increases risk for dementia in pure synucleinopathies.

Objective: To test for an association between the apolipoprotein E (APOE) ϵ4 allele and dementias with synucleinopathy.

Design: Genetic case-control association study.

Setting: Academic research.

Risk prediction for complex diseases: application to Parkinson disease.

Purpose: The aim of this study was to evaluate the risk of Parkinson disease using clinical and demographic data alone and when combined with information from genes associated with Parkinson disease.

Methods: A total of 1,967 participants in the dbGAP NeuroGenetics Research Consortium data set were included. Single-nucleotide polymorphisms associated with Parkinson disease at a genome-wide significance level in previous genome-wide association studies were included in risk prediction.

Common variation in the LRRK2 gene is a risk factor for Parkinson's disease.

Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear.

Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .

GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology.

Objectives: Mutations in the GBA gene occur in 7% of patients with Parkinson disease (PD) and are a well-established susceptibility factor for PD, which is characterized by Lewy body disease (LBD) neuropathologic changes (LBDNCs). We sought to determine whether GBA influences risk of dementia with LBDNCs, Alzheimer disease (AD) neuropathologic changes (ADNCs), or both.

Methods: We screened the entire GBA coding region for mutations in controls and in subjects with dementia and LBDNCs and no or low levels of ADNCs (pure dementia with Lewy bodies [pDLB]), LBDNCs and high-level ADNCs (LBD-AD), and high-level ADNCs but without LBDNCs (AD).

Multivariate linkage scan for metabolic syndrome traits in families with type 2 diabetes.

The purpose of this study was to evaluate evidence for linkage to interrelated quantitative features of the metabolic syndrome (MetS). Data on eight quantitative MetS traits (body weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein (HDL) cholesterol, triglycerides (TGs), and fasting glucose and insulin measurements) and a 10 cM genome scan were available for 78 white families (n = 532 subjects). These data were used to conduct multipoint, multivariate linkage analyses, including tests for coincident linkage and complete pleiotropy.

Genome-wide linkage scan for the metabolic syndrome: the GENNID study.

In the United States, the metabolic syndrome (MetS) constitutes a major public health problem with over 47 million persons meeting clinical criteria for MetS. Numerous studies have suggested genetic susceptibility to MetS. The goals of this study were (i) to identify susceptibility loci for MetS in well-characterized families with type 2 diabetes (T2D) in four ethnic groups and (ii) to determine whether evidence for linkage varies across the four groups.