Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005

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The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.

SUMMARY In a consecutive medicolegal necropsy series benign hepatic tumours and tumour like conditions occurred in 52% of the 95 men aged 35-69 years. The incidence increased with age, mainly due to small bile duct tumours (n = 26; mean age 56-7 years; p <0 01; mean size 1'3 mm). The next most common tumours were cavernous hemangiomas (n = 19; mean age 53 9 years; mean size 5-2 mm) that were not related to age. Focal nodular hyperplasia (n = 3; mean size 8-0 mm) tended to occur in a younger age group (mean age 40 3 years; p < 0-00 1). Multiple bile duct tumours were present in 46% and hemangiomas in 50% of the men studied. Liver cell adenoma, nodular regenerative hyperplasia, and peliosis hepatis were incidental findings (one case of each). Nodular regenerative hyperplasia was associated with the consumption of alcohol and a total dose of 21 5 g of testosterone.These In total 66 3% of the deaths were caused by disease. The low incidence of death due to neoplasms (1%) and the high proportion of intoxications due to alcohol or a combination of alcohol and drugs (I 5-8%), as well as the high proportion of other violent deaths (17 9%), characterised the medicolegal nature of the series. LIVER SPECIMENSEach liver was sliced into 1-2 cm sections after a careful search for capsular lesions or tumours. The cut surfaces were inspected under optimal illumination, and blocks (n = 505) were taken from suspect areas for histology. In addition, routine blocks were taken: one from the surface of the right liver lobe at the usual site of liver biopsy, one from the inferior edge of the right lobe at the usual site of surgical biopsy, and one from the surface of the left lobe. These blocks (n = 285) were examined without knowledge of the results of the study on the suspected lesions. Sections were cut and stained with hematoxylin and eosin and haematoxylin and van Gieson. The maximum width 183 on 12 May 2018 by guest. Protected by copyright.

Sequence variation in mitochondrial DNA (mtDNA) may cause slight differences both in the functioning of the respiratory chain and in free radical production, and an association between certain mtDNA haplogroups and longevity has been suggested. In order to determine further the role of mtDNA in longevity, we studied the frequencies of mtDNA haplogroups and haplogroup clusters among elderly subjects and controls in a Finnish population. Samples were obtained from 225 persons aged 90-91 years (Vitality 90+) and from 400 middle-aged controls and 257 infants. MtDNA haplogroups were determined by restriction fragment length polymorphism. The haplogroup frequencies of the Vitality 90+ group differed from both those of the middle-aged controls ( P=0.01) and the infants ( P=0.00005), haplogroup H being less frequent than among the middle-aged subjects ( P=0.001) and infants ( P=0.00001), whereas haplogroups U and J were more frequent. Haplogroup clusters also differed between Vitality 90+ and both the middle-aged subjects ( P=0.002) and infants ( P=0.00001), the frequency of haplogroup cluster HV being lower in the former and that of UK and WIX being higher. These data suggest an association between certain mtDNA haplogroups or haplogroup clusters and longevity. Furthermore, our data appear to favour the presence of advantageous polymorphisms and support a role for mitochondria and mtDNA in the degenerative processes involved in ageing.