Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Epicondylitis is a common disorder of the arm, yet the role of individual- and work-related factors has not been addressed in a population study. The aims of this study were to estimate the prevalence of lateral and medial epicondylitis and to investigate their risk factors. The target population of this study comprised a representative sample of people aged 30-64 years residing in Finland during 2000-2001. Of the 5,871 subjects, 4,783 (81.5%) were included in this study. The prevalence of definite lateral epicondylitis was 1.3%, and that of medial epicondylitis was 0.4%. The prevalence did not differ between men and women and was highest in subjects aged 45-54 years. Current smoking (adjusted odds ratio (OR) = 3.4, 95% confidence interval (CI): 1.4, 8.3) and former smoking (OR = 3.0, 95% CI: 1.3, 6.6) were associated with definite lateral epicondylitis. An interaction (p = 0.002) was found between repetitive movements of the arms and forceful activities for the risk of possible or definite lateral epicondylitis (for both repetitive and forceful activities vs. no such activity: OR = 5.6, 95% CI: 1.9, 16.5). Smoking, obesity, repetitive movements, and forceful activities independently of each other showed significant associations with medial epicondylitis. Epicondylitis is relatively common among working-age individuals in the general population. Physical load factors, smoking, and obesity are strong determinants of epicondylitis.

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 (FEV1) and the ratio of FEV1 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 ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Objectives-To determine optimal hand-grip strength cut-points for increased likelihood for mobility limitation among older people and to study whether these cut-points differ according to body mass index (BMI).Design and setting-Cross-sectional analysis of data collected in the Finnish population-based Health 2000 Survey.Participants and measurements-1 084 men and 1 562 women aged 55 years and older with complete data on anthropometry, hand-grip strength and self-reported mobility. Mobility limitation was defined as difficulties in walking 0.5-km or climbing stairs. Receiver Operating Characteristics analysis was used to estimate hand-grip strength cut-points for increased likelihood for mobility limitation.Results-The overall hand-grip strength cut-points for increased likelihood for mobility limitation were 37 kg (sensitivity 62% and specificity 76%) for men and 21 kg (67% and 73%) for women. Hand-grip strength by BMI interaction on mobility limitation was significant among men (p = 0.022), while no such interaction was observed among women (p = 0.156). Among men, most optimal cut-offs were 33 kg (73% and 79%) for normal-weight men, 39 kg (67% and 71%) for overweight men and 40 kg (57% and 68%) for obese men. Among women, BMI-specific handgrip strength cut-off values did not markedly increase accuracy over the overall cut-off value.Conclusion-Hand-grip strength test is a useful tool to identify persons with increased risk for mobility limitation. Among men, the hand-grip strength cut-points for mobility increased along with BMI, while among women only one hand-grip strength threshold was identified.

Musculoskeletal pain frequently occurs without particular clinical findings. Pain per se may be determined by factors other than those indicating a clinical disorder. The authors examined the prevalence and determinants of clinically diagnosed chronic rotator cuff tendinitis and self-reported nonspecific shoulder pain. The Health 2000 survey, carried out in 2000-2001 in Finland, included a nationally representative sample of 8,028 persons aged 30 years or more. In the present study, analyses were restricted to subjects aged 30-64 years who had held a job during the preceding 12 months. The prevalences of chronic rotator cuff tendinitis and nonspecific shoulder pain were 2.0% (78 of 3,909 subjects) and 12% (410 of 3,525 subjects), respectively. Nonspecific pain was related to burnout (adjusted odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.4, 2.2), depression (among women, the adjusted OR was 1.8 (95% CI: 1.1, 2.9) for mild depression and 3.0 (95% CI: 1.6, 5.6) for severe depression), and inability to express one's feelings (alexithymia) (adjusted OR = 1.6, 95% CI: 1.1, 2.5). However, these factors were not associated with chronic rotator cuff tendinitis, determinants of which were work-related cumulative loading on the shoulder, age, and insulin-dependent diabetes mellitus (adjusted OR = 8.8, 95% CI: 1.9, 40.3). The determinants of specific musculoskeletal disorders differ from those of subjective complaints without clinical findings. Such complaints may be indicators of adverse psychological and psychosocial factors rather than the presence of an underlying pathologic condition.

Major dietary patterns were studied for the ability to predict type 2 diabetes mellitus in a cohort of 4,304 Finnish men and women aged 40-69 years and free of diabetes at baseline in 1967-1972. Factor analysis was used to identify dietary patterns from dietary data that were collected using a 1-year dietary history interview. A total of 383 incident cases of type 2 diabetes occurred during a 23-year follow-up. Two major dietary patterns were identified. The pattern labeled "prudent" was characterized by higher consumption of fruits and vegetables, and the pattern labeled "conservative" was characterized by consumption of butter, potatoes, and whole milk. The relative risks (adjusted for nondietary confounders) between the extreme quartiles of the pattern scores were 0.72 (95% confidence interval: 0.53, 0.97; p(trend) = 0.03) for the prudent pattern and 1.49 (95% confidence interval: 1.11, 2.00; p(trend) = 0.01) for the conservative pattern. Thus, the prudent dietary pattern score was associated with a reduced risk and the conservative pattern score was associated with an increased risk of type 2 diabetes. In light of these results, it appears conceivable that the risk of developing type 2 diabetes can be reduced by changing dietary patterns.