0000000000134181
AUTHOR
Markku Heliövaara
Genome-wide association study identifies five loci associated with lung function
Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and co…
Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of RO…
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may p…
Association study of MMP8 gene in osteoarthritis.
Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The chi(2) test for …
Long-Term Determinants of Muscle Strength Decline: Prospective Evidence from the 22-Year Mini-Finland Follow-Up Survey
Objectives: To examine long-term changes in handgrip strength and the factors predicting handgrip strength decline. Design: Longitudinal cohort study with 22 years of follow-up. Setting: Population-based Mini-Finland Health Examination Survey in Finland. Participants: Nine hundred sixty-three men and women aged 30 to 73 at baseline. Measurements: Handgrip strength was measured using a handheld dynamometer at baseline and follow-up. Information on potential risk factors, namely lifestyle and chronic conditions, and their changes throughout the follow-up were based on health interviews. Results: Based on linear mixed-effect models, midlife physically strenuous work, excess body weight, smokin…
The Mediating Role of C-Reactive Protein and Handgrip Strength Between Obesity and Walking Limitation
OBJECTIVES: To study the association between different obesity indicators and walking limitation and to examine the role of C-reactive protein (CRP) and handgrip strength in that association. DESIGN: A cross-sectional, population-based study. SETTING: The Health 2000 Survey with a representative sample of the Finnish population. PARTICIPANTS: Subjects aged 55 and older with complete data on body composition, CRP, handgrip strength, and walking limitation (N=2,208). MEASUREMENTS: Body composition, anthropometrics, CRP, medical conditions, handgrip strength, and maximal walking speed were measured in the health examination. Walking limitation was defined as maximal walking speed less than 1.2…
Association between Obesity History and Hand Grip Strength in Older Adults-Exploring the Roles of Inflammation and Insulin Resistance as Mediating Factors
Background: To examine the association between obesity history and hand grip strength, and whether the association is partly explained by subclinical inflammation and insulin resistance. Methods:Data are from 2,021 men and women aged 55 years and older participating in the representative population-based Health 2000 Survey in Finland. Body mass and body height, maximal hand grip strength, C-reactive protein, and insulin resistance based on homeostasis model assessment (HOMA-IR) were measured in a health examination. Recalled weight at 20, 30, 40, and 50 years of age were recorded to obtain a hierarchical classification of obesity history. Obesity was defined as body mass index ≥ 30 kg/m2. R…
Hand-Grip Strength Cut Points to Screen Older Persons at Risk for Mobility Limitation
Objectives To determine optimal hand-grip strength cut points for likelihood of mobility limitation in older people and to study whether these cut points differ according to body mass index (BMI). Design Cross-sectional analysis of data. Setting Data collected in the Finnish population-based Health 2000 Survey. Participants One thousand eighty-four men and 1,562 women aged 55 and older with complete data on anthropometry, hand-grip strength and self-reported mobility. Measurements Mobility limitation was defined as difficulty walking 0.5 km or climbing stairs. Receiver operating characteristic analysis was used to estimate hand-grip strength cut points for likelihood of mobility limitation.…
Genome-wide association analysis identifies six new loci associated with forced vital capacity
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispani…
Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies
BACKGROUND: The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica. METHODS: We included 4 Finnish prospective cohort studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital discharge register data. We conducted a random-effects individual participant data meta-analysis. RESULTS: After adjustment for confounding facto…