@article {8823, title = {Genome-wide Association Study of Parental Life Span.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {72}, year = {2017}, month = {2017 Oct 01}, pages = {1407-1410}, abstract = {

Background: Having longer lived parents has been shown to be an important predictor of health trajectories and life span. As such, parental life span is an important phenotype that may uncover genes that affect longevity.

Methods: A genome-wide association study of parental life span in participants of European and African ancestry from the Health and Retirement Study was conducted.

Results: A genome-wide significant association was observed for rs35715456 (log10BF = 6.3) on chromosome 18 for the dichotomous trait of having at least one long-lived parent versus not having any long-lived parent. This association was not replicated in an independent sample from the InCHIANTI and Framingham Heart Study. The most significant association among single nucleotide polymorphisms in longevity candidate genes (APOE, MINIPP1, FOXO3, EBF1, CAMKIV, and OTOL1) was observed in the EBF1 gene region (rs17056207, p = .0002).

Conclusions: A promising genetic signal for parental life span was identified but was not replicated in independent samples.

}, keywords = {Aged, Aged, 80 and over, Chromosomes, Human, Pair 18, Female, Genome-Wide Association Study, Humans, Longevity, Male, Middle Aged, Parents, Phenotype, Polymorphism, Single Nucleotide, Trans-Activators}, issn = {1758-535X}, doi = {10.1093/gerona/glw206}, url = {http://biomedgerontology.oxfordjournals.org/lookup/doi/10.1093/gerona/glw206https://academic.oup.com/biomedgerontology/article/2422264/Genomewide-Association-Study-of-Parental-Life-Span}, author = {Toshiko Tanaka and Ambarish Dutta and Luke C Pilling and Xue, Luting and Kathryn L Lunetta and Joanne M Murabito and Bandinelli, Stefania and Robert B Wallace and David Melzer and Luigi Ferrucci} } @article {9442, title = {Human longevity: 25 genetic loci associated in 389,166 UK biobank participants}, journal = {Aging}, volume = {9}, year = {2017}, pages = {2504-2520}, abstract = {We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers{\textquoteright} and fathers{\textquoteright} attained age, 10 loci were associated (p<5*10(-8)), including 8 previously identified for traits including survival, Alzheimer{\textquoteright}s and cardiovascular disease. Of these, 4 were also associated with longest 10\% survival (mother{\textquoteright}s age >= 90 years, father{\textquoteright}s >= 87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother{\textquoteright}s age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.}, keywords = {Cross-National, Genetics, Genome, GWAS, Longevity}, doi = {10.18632/aging.101334}, url = {http://www.aging-us.com/article/101334/texthttp://www.aging-us.com/article/101334/text?_escaped_fragment_=}, author = {Luke C Pilling and Kuo, Chia-Ling and Sicinski, Kamil and Tamosauskaite, Jone and George A Kuchel and Lorna W. Harries and Herd, Pamela and Robert B Wallace and Luigi Ferrucci and David Melzer} } @article {8534, title = {Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.}, journal = {Psychol Med}, volume = {46}, year = {2016}, month = {2016 06}, pages = {1613-23}, abstract = {

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.

METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).

RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 {\texttimes} 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 {\texttimes} 10-6) with evidence of heterogeneity.

CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

}, keywords = {depression, Depressive Disorder, Major, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptor, Melatonin, MT1, Somatoform Disorders}, issn = {1469-8978}, doi = {10.1017/S0033291715002081}, url = {https://www.ncbi.nlm.nih.gov/pubmed/26997408}, author = {Demirkan, A and J. Lahti and Nese Direk and Viktorin, A. and Kathryn L Lunetta and Antonio Terracciano and Michael A Nalls and Toshiko Tanaka and Karin Hek and Myriam Fornage and J{\"u}rgen Wellmann and Marilyn C Cornelis and Ollila, H. M. and Lei Yu and Luke C Pilling and Isaacs, A and Aarno Palotie and Wei Vivian Zhuang and Alan B Zonderman and Jessica Faul and Angelina R Sutin and Osorio Meirelles and Mulas, A and Hofman, A and Andr{\'e} G Uitterlinden and Fernando Rivadeneira and Markus Perola and Wei Zhao and Veikko Salomaa and Kristine Yaffe and Luik, A I and Yongmei Liu and Ding, J and Paul Lichtenstein and Land{\'e}n, M and Elisabeth Widen and David R Weir and David J Llewellyn and Murray, A and Sharon L R Kardia and Johan G Eriksson and Karestan C Koenen and Patrik K E Magnusson and Luigi Ferrucci and Thomas H Mosley and Francesco Cucca and Ben A Oostra and David A Bennett and Paunio, T. and Klaus Berger and Tamara B Harris and Nancy L Pedersen and Joanne M Murabito and Henning Tiemeier and Cornelia M van Duijn and Katri R{\"a}ikk{\"o}nen} }