Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association (GWA) meta-analysis based in 135,458 cases and 344,901 control, We identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression, and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relations of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine and define the basis of major depression and imply a continuous measure of risk underlies the clinical phenotype.

The moderate PPV suggests that the HADS is best used as a screening questionnaire and not as a 'case-identifier' for psychiatric disorder or depression.

Abstract-Atherosclerosis and osteoporosis are major causes of morbidity and mortality in postmenopausal women and have been suggested to be associated. No study has examined whether progression of atherosclerotic calcification is associated with bone loss. In the present study, we examined progression of aortic calcification, diagnosed by radiographic detection of calcified deposits in the abdominal aorta, in relation to metacarpal bone loss, as assessed by metacarpal radiogrammetry, during menopause. Initially premenopausal women (nϭ236), aged 45 to 57 years at baseline, were followed for 9 years. We additionally assessed the cross-sectional association between the extent of aortic calcification and metacarpal bone mass and density in 720 postmenopausal women. Twenty-five percent of women going through menopause showed progression of aortic calcification. The average loss of metacarpal bone mass among women with progression of aortic calcification was 3.2 mm 2 , and their loss of metacarpal bone density was 7.2 mm 2 %, whereas in women without progression of aortic calcification, these losses were 2.0 mm 2 and 5.6 mm 2 %, respectively, adjusted for age and years of follow-up (PϽ0.05). Additional adjustment for age at menopause, body mass index, blood pressure, smoking, diabetes mellitus, and use of hormone replacement therapy, thiazide, and loop diuretics did not influence these results. In postmenopausal women, a graded inverse cross-sectional association between the extent of aortic calcification and metacarpal bone mass and density was found. In conclusion, our results indicate that progression of atherosclerotic calcification is associated with increased bone loss in women during menopause. Key Words: atherosclerosis Ⅲ vascular calcification Ⅲ osteoporosis Ⅲ menopause C ardiovascular disease and osteoporosis are major causes of morbidity and mortality in postmenopausal women 1,2 and are generally considered unrelated. Several studies, however, indicate that atherosclerosis and osteoporosis are associated. [3][4][5][6][7][8][9][10] Calcification is a common feature of atherosclerotic plaques and is regulated in a way similar to bone mineralization. [11][12][13][14][15][16] The relation of vascular calcification to the pathogenesis of atherosclerosis and plaque rupture is not clear yet, but data indicate that moderate calcification of plaques contributes to vascular morbidity and mortality. [17][18][19][20] Several cross-sectional studies have been conducted on the association between atherosclerotic calcification and osteoporosis among elderly women. [3][4][5][6][7][8][21][22][23] Most of these studies found an association, 3-8 although some did not. [21][22][23] Potential confounding factors other than age have not been taken into account in most of these studies. [3][4][5]8,21,22 No study examined whether progression of atherosclerotic calcification is associated with bone loss. Because the prevalence of atherosclerosis and osteoporosis increases from menopause onward, 24,25 the change from the premenopaus...

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