@article {1107, title = {NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.}, journal = {PLoS Genet}, volume = {5}, year = {2009}, month = {2009 Jun}, pages = {e1000539}, abstract = {

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4x10(-7))]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3x10(-8) for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4x10(-6), 0.024 z-score units (0.10 kg/m(2)) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95\% CI 1.07-1.19; p = 3.2x10(-5) per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.

}, keywords = {Aged, Body Mass Index, Cohort Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Nerve Tissue Proteins, Obesity, Polymorphism, Single Nucleotide, Waist Circumference}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1000539}, author = {Heard-Costa, Nancy L and Zillikens, M Carola and Monda, Keri L and Johansson, Asa and Harris, Tamara B and Fu, Mao and Haritunians, Talin and Feitosa, Mary F and Aspelund, Thor and Eiriksdottir, Gudny and Garcia, Melissa and Launer, Lenore J and Smith, Albert V and Mitchell, Braxton D and McArdle, Patrick F and Shuldiner, Alan R and Bielinski, Suzette J and Boerwinkle, Eric and Brancati, Fred and Demerath, Ellen W and Pankow, James S and Arnold, Alice M and Chen, Yii-Der Ida and Glazer, Nicole L and McKnight, Barbara and Psaty, Bruce M and Rotter, Jerome I and Amin, Najaf and Campbell, Harry and Gyllensten, Ulf and Pattaro, Cristian and Pramstaller, Peter P and Rudan, Igor and Struchalin, Maksim and Vitart, Veronique and Gao, Xiaoyi and Kraja, Aldi and Province, Michael A and Zhang, Qunyuan and Atwood, Larry D and Dupuis, Jos{\'e}e and Hirschhorn, Joel N and Jaquish, Cashell E and O{\textquoteright}Donnell, Christopher J and Vasan, Ramachandran S and White, Charles C and Aulchenko, Yurii S and Estrada, Karol and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Witteman, Jacqueline C M and Oostra, Ben A and Kaplan, Robert C and Gudnason, Vilmundur and O{\textquoteright}Connell, Jeffrey R and Borecki, Ingrid B and van Duijn, Cornelia M and Cupples, L Adrienne and Fox, Caroline S and North, Kari E} } @article {1307, title = {A genome-wide association study of aging.}, journal = {Neurobiol Aging}, volume = {32}, year = {2011}, month = {2011 Nov}, pages = {2109.e15-28}, abstract = {

Human longevity and healthy aging show moderate heritability (20\%-50\%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 {\texttimes} 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer{\textquoteright}s disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

}, keywords = {Aging, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Longevity}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2011.05.026}, author = {Walter, Stefan and Atzmon, Gil and Demerath, Ellen W and Garcia, Melissa E and Kaplan, Robert C and Kumari, Meena and Lunetta, Kathryn L and Milaneschi, Yuri and Tanaka, Toshiko and Tranah, Gregory J and V{\"o}lker, Uwe and Yu, Lei and Arnold, Alice and Benjamin, Emelia J and Biffar, Reiner and Buchman, Aron S and Boerwinkle, Eric and Couper, David and De Jager, Philip L and Evans, Denis A and Harris, Tamara B and Hoffmann, Wolfgang and Hofman, Albert and Karasik, David and Kiel, Douglas P and Kocher, Thomas and Kuningas, Maris and Launer, Lenore J and Lohman, Kurt K and Lutsey, Pamela L and Mackenbach, Johan and Marciante, Kristin and Psaty, Bruce M and Reiman, Eric M and Rotter, Jerome I and Seshadri, Sudha and Shardell, Michelle D and Smith, Albert V and van Duijn, Cornelia and Walston, Jeremy and Zillikens, M Carola and Bandinelli, Stefania and Baumeister, Sebastian E and Bennett, David A and Ferrucci, Luigi and Gudnason, Vilmundur and Kivimaki, Mika and Liu, Yongmei and Murabito, Joanne M and Newman, Anne B and Tiemeier, Henning and Franceschini, Nora} } @article {1360, title = {Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.}, journal = {Nat Genet}, volume = {44}, year = {2012}, month = {2012 Jan 22}, pages = {260-8}, abstract = {

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 {\texttimes} 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

}, keywords = {Age Factors, DNA Helicases, DNA Polymerase gamma, DNA Primase, DNA Repair, DNA Repair Enzymes, DNA-Directed DNA Polymerase, European Continental Ancestry Group, Exodeoxyribonucleases, Female, Genetic Loci, Genome-Wide Association Study, Humans, Immunity, Menopause, Polymorphism, Single Nucleotide, Proteins}, issn = {1546-1718}, doi = {10.1038/ng.1051}, author = {Stolk, Lisette and Perry, John R B and Chasman, Daniel I and He, Chunyan and Mangino, Massimo and Sulem, Patrick and Barbalic, Maja and Broer, Linda and Byrne, Enda M and Ernst, Florian and Esko, T{\~o}nu and Franceschini, Nora and Gudbjartsson, Daniel F and Hottenga, Jouke-Jan and Kraft, Peter and McArdle, Patrick F and Porcu, Eleonora and Shin, So-Youn and Smith, Albert V and van Wingerden, Sophie and Zhai, Guangju and Zhuang, Wei V and Albrecht, Eva and Alizadeh, Behrooz Z and Aspelund, Thor and Bandinelli, Stefania and Lauc, Lovorka Barac and Beckmann, Jacques S and Boban, Mladen and Boerwinkle, Eric and Broekmans, Frank J and Burri, Andrea and Campbell, Harry and Chanock, Stephen J and Chen, Constance and Cornelis, Marilyn C and Corre, Tanguy and Coviello, Andrea D and D{\textquoteright}Adamo, Pio and Davies, Gail and de Faire, Ulf and de Geus, Eco J C and Deary, Ian J and Dedoussis, George V Z and Deloukas, Panagiotis and Ebrahim, Shah and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan G and Fauser, Bart C J M and Ferreli, Liana and Ferrucci, Luigi and Fischer, Krista and Folsom, Aaron R and Garcia, Melissa E and Gasparini, Paolo and Gieger, Christian and Glazer, Nicole and Grobbee, Diederick E and Hall, Per and Haller, Toomas and Hankinson, Susan E and Hass, Merli and Hayward, Caroline and Heath, Andrew C and Hofman, Albert and Ingelsson, Erik and Janssens, A Cecile J W and Johnson, Andrew D and Karasik, David and Kardia, Sharon L R and Keyzer, Jules and Kiel, Douglas P and Kolcic, Ivana and Kutalik, Zolt{\'a}n and Lahti, Jari and Lai, Sandra and Laisk, Triin and Laven, Joop S E and Lawlor, Debbie A and Liu, Jianjun and Lopez, Lorna M and Louwers, Yvonne V and Magnusson, Patrik K E and Marongiu, Mara and Martin, Nicholas G and Klaric, Irena Martinovic and Masciullo, Corrado and McKnight, Barbara and Medland, Sarah E and Melzer, David and Mooser, Vincent and Navarro, Pau and Newman, Anne B and Nyholt, Dale R and Onland-Moret, N Charlotte and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peeters, Petra H M and Pistis, Giorgio and Plump, Andrew S and Polasek, Ozren and Pop, Victor J M and Psaty, Bruce M and R{\"a}ikk{\"o}nen, Katri and Rehnberg, Emil and Rotter, Jerome I and Rudan, Igor and Sala, Cinzia and Salumets, Andres and Scuteri, Angelo and Singleton, Andrew and Smith, Jennifer A and Snieder, Harold and Soranzo, Nicole and Stacey, Simon N and Starr, John M and Stathopoulou, Maria G and Stirrups, Kathleen and Stolk, Ronald P and Styrkarsdottir, Unnur and Sun, Yan V and Tenesa, Albert and Thorand, Barbara and Toniolo, Daniela and Tryggvadottir, Laufey and Tsui, Kim and Ulivi, Sheila and van Dam, Rob M and van der Schouw, Yvonne T and van Gils, Carla H and van Nierop, Peter and Vink, Jacqueline M and Visscher, Peter M and Voorhuis, Marlies and Waeber, G{\'e}rard and Wallaschofski, Henri and Wichmann, H Erich and Widen, Elisabeth and Wijnands-van Gent, Colette J M and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wright, Alan F and Yerges-Armstrong, Laura M and Zemunik, Tatijana and Zgaga, Lina and Zillikens, M Carola and Zygmunt, Marek and Arnold, Alice M and Boomsma, Dorret I and Buring, Julie E and Crisponi, Laura and Demerath, Ellen W and Gudnason, Vilmundur and Harris, Tamara B and Hu, Frank B and Hunter, David J and Launer, Lenore J and Metspalu, Andres and Montgomery, Grant W and Oostra, Ben A and Ridker, Paul M and Sanna, Serena and Schlessinger, David and Spector, Tim D and Stefansson, Kari and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and Uda, Manuela and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and V{\"o}lzke, Henry and Murray, Anna and Murabito, Joanne M and Visser, Jenny A and Lunetta, Kathryn L} } @article {1544, title = {Ultraconserved elements in the human genome: association and transmission analyses of highly constrained single-nucleotide polymorphisms.}, journal = {Genetics}, volume = {192}, year = {2012}, month = {2012 Sep}, pages = {253-66}, abstract = {

Ultraconserved elements in the human genome likely harbor important biological functions as they are dosage sensitive and are able to direct tissue-specific expression. Because they are under purifying selection, variants in these elements may have a lower frequency in the population but a higher likelihood of association with complex traits. We tested a set of highly constrained SNPs (hcSNPs) distributed genome-wide among ultraconserved and nearly ultraconserved elements for association with seven traits related to reproductive (age at natural menopause, number of children, age at first child, and age at last child) and overall [longevity, body mass index (BMI), and height] fitness. Using up to 24,047 European-American samples from the National Heart, Lung, and Blood Institute Candidate Gene Association Resource (CARe), we observed an excess of associations with BMI and height. In an independent replication panel the most strongly associated SNPs showed an 8.4-fold enrichment of associations at the nominal level, including three variants in previously identified loci and one in a locus (DENND1A) previously shown to be associated with polycystic ovary syndrome. Finally, using 1430 family trios, we showed that the transmissions from heterozygous parents to offspring of the derived alleles of rare (frequency <= 0.5\%) hcSNPs are not biased, particularly after adjusting for the rates of genotype missingness and error in the data. The lack of transmission bias ruled out an immediately and strongly deleterious effect due to the rare derived alleles, consistent with the observation that mice homozygous for the deletion of ultraconserved elements showed no overt phenotype. Our study also illustrated the importance of carefully modeling potential technical confounders when analyzing genotype data of rare variants.

}, keywords = {Alleles, Animals, Body Height, Body Mass Index, Child, Conserved Sequence, Dogs, Evolution, Molecular, Female, Genetic Fitness, Genetic Variation, Genome, Human, Genotype, Humans, Inheritance Patterns, Male, Mice, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Rats, Reproduction, Young Adult}, issn = {1943-2631}, doi = {10.1534/genetics.112.141945}, author = {Chiang, Charleston W K and Liu, Ching-Ti and Lettre, Guillaume and Lange, Leslie A and Jorgensen, Neal W and Keating, Brendan J and Vedantam, Sailaja and Nock, Nora L and Franceschini, Nora and Reiner, Alex P and Demerath, Ellen W and Boerwinkle, Eric and Rotter, Jerome I and Wilson, James G and North, Kari E and Papanicolaou, George J and Cupples, L Adrienne and Murabito, Joanne M and Hirschhorn, Joel N} } @article {6287, title = {Genome-wide association of body fat distribution in African ancestry populations suggests new loci.}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013}, pages = {e1003681}, abstract = {

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 {\texttimes} 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24{\texttimes}10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48{\texttimes}10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 {\texttimes} 10(-8); RREB1: p = 5.7 {\texttimes} 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

}, keywords = {Adiposity, African Continental Ancestry Group, Body Fat Distribution, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Waist-Hip Ratio}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003681}, author = {Liu, Ching-Ti and Monda, Keri L and Taylor, Kira C and Lange, Leslie and Demerath, Ellen W and Palmas, Walter and Wojczynski, Mary K and Ellis, Jaclyn C and Vitolins, Mara Z and Liu, Simin and Papanicolaou, George J and Irvin, Marguerite R and Xue, Luting and Griffin, Paula J and Nalls, Michael A and Adeyemo, Adebowale and Liu, Jiankang and Li, Guo and Ruiz-Narvaez, Edward A and Chen, Wei-Min and Chen, Fang and Henderson, Brian E and Millikan, Robert C and Ambrosone, Christine B and Strom, Sara S and Guo, Xiuqing and Andrews, Jeanette S and Sun, Yan V and Mosley, Thomas H and Yanek, Lisa R and Shriner, Daniel and Haritunians, Talin and Rotter, Jerome I and Speliotes, Elizabeth K and Smith, Megan and Rosenberg, Lynn and Mychaleckyj, Josyf and Nayak, Uma and Spruill, Ida and Garvey, W Timothy and Pettaway, Curtis and Nyante, Sarah and Bandera, Elisa V and Britton, Angela F and Zonderman, Alan B and Rasmussen-Torvik, Laura J and Chen, Yii-Der Ida and Ding, Jingzhong and Lohman, Kurt and Kritchevsky, Stephen B and Zhao, Wei and Peyser, Patricia A and Kardia, Sharon L R and Kabagambe, Edmond and Broeckel, Ulrich and Chen, Guanjie and Zhou, Jie and Wassertheil-Smoller, Sylvia and Neuhouser, Marian L and Rampersaud, Evadnie and Psaty, Bruce and Kooperberg, Charles and Manson, JoAnn E and Kuller, Lewis H and Ochs-Balcom, Heather M and Johnson, Karen C and Sucheston, Lara and Ordovas, Jose M and Palmer, Julie R and Haiman, Christopher A and McKnight, Barbara and Howard, Barbara V and Becker, Diane M and Bielak, Lawrence F and Liu, Yongmei and Allison, Matthew A and Grant, Struan F A and Burke, Gregory L and Patel, Sanjay R and Schreiner, Pamela J and Borecki, Ingrid B and Evans, Michele K and Taylor, Herman and Sale, Mich{\`e}le M and Howard, Virginia and Carlson, Christopher S and Rotimi, Charles N and Cushman, Mary and Harris, Tamara B and Reiner, Alexander P and Cupples, L Adrienne and North, Kari E and Fox, Caroline S} } @article {6153, title = {A genome-wide association study of early menopause and the combined impact of identified variants.}, journal = {Hum Mol Genet}, volume = {22}, year = {2013}, month = {2013 Apr 01}, pages = {1465-72}, abstract = {

Early menopause (EM) affects up to 10\% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for \~{}30\% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.

}, keywords = {Case-Control Studies, Female, Gene Frequency, Genome-Wide Association Study, Humans, Menopause, Premature, Polymorphism, Single Nucleotide, Primary Ovarian Insufficiency, Quantitative Trait Loci, Risk}, issn = {1460-2083}, doi = {10.1093/hmg/dds551}, author = {Perry, John R B and Corre, Tanguy and Esko, T{\~o}nu and Chasman, Daniel I and Fischer, Krista and Franceschini, Nora and He, Chunyan and Kutalik, Zolt{\'a}n and Mangino, Massimo and Rose, Lynda M and Vernon Smith, Albert and Stolk, Lisette and Sulem, Patrick and Weedon, Michael N and Zhuang, Wei V and Arnold, Alice and Ashworth, Alan and Bergmann, Sven and Buring, Julie E and Burri, Andrea and Chen, Constance and Cornelis, Marilyn C and Couper, David J and Goodarzi, Mark O and Gudnason, Vilmundur and Harris, Tamara and Hofman, Albert and Jones, Michael and Kraft, Peter and Launer, Lenore and Laven, Joop S E and Li, Guo and McKnight, Barbara and Masciullo, Corrado and Milani, Lili and Orr, Nicholas and Psaty, Bruce M and Ridker, Paul M and Rivadeneira, Fernando and Sala, Cinzia and Salumets, Andres and Schoemaker, Minouk and Traglia, Michela and Waeber, G{\'e}rard and Chanock, Stephen J and Demerath, Ellen W and Garcia, Melissa and Hankinson, Susan E and Hu, Frank B and Hunter, David J and Lunetta, Kathryn L and Metspalu, Andres and Montgomery, Grant W and Murabito, Joanne M and Newman, Anne B and Ong, Ken K and Spector, Tim D and Stefansson, Kari and Swerdlow, Anthony J and Thorsteinsdottir, Unnur and van Dam, Rob M and Uitterlinden, Andr{\'e} G and Visser, Jenny A and Vollenweider, Peter and Toniolo, Daniela and Murray, Anna} } @article {6368, title = {Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 May 01}, pages = {2498-510}, abstract = {

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI{\textquoteright}s Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes \~{}50 000 cosmopolitan tagged SNPs across \~{}2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 {\texttimes} 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β {\textpm} SE, 0.048 {\textpm} 0.008, P = 7.7 {\texttimes} 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 {\textpm} 0.008, P = 2.9 {\texttimes} 10(-7)) and rs936108-C in PEMT (β = 0.035 {\textpm} 0.007, P = 1.9 {\texttimes} 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 {\textpm} 0.02, P = 1.9 {\texttimes} 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 {\textpm} 0.01, P = 2.2 {\texttimes} 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

}, keywords = {Adiposity, Adult, Aged, Aged, 80 and over, Body Mass Index, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Waist Circumference, Waist-Hip Ratio, Young Adult}, issn = {1460-2083}, doi = {10.1093/hmg/ddt626}, author = {Yoneyama, Sachiko and Guo, Yiran and Lanktree, Matthew B and Barnes, Michael R and Elbers, Clara C and Karczewski, Konrad J and Padmanabhan, Sandosh and Bauer, Florianne and Baumert, Jens and Beitelshees, Amber and Berenson, Gerald S and Boer, Jolanda M A and Burke, Gregory and Cade, Brian and Chen, Wei and Cooper-Dehoff, Rhonda M and Gaunt, Tom R and Gieger, Christian and Gong, Yan and Gorski, Mathias and Heard-Costa, Nancy and Johnson, Toby and Lamonte, Michael J and McDonough, Caitrin and Monda, Keri L and Onland-Moret, N Charlotte and Nelson, Christopher P and O{\textquoteright}Connell, Jeffrey R and Ordovas, Jose and Peter, Inga and Peters, Annette and Shaffer, Jonathan and Shen, Haiqinq and Smith, Erin and Speilotes, Liz and Thomas, Fridtjof and Thorand, Barbara and Monique Verschuren, W M and Anand, Sonia S and Dominiczak, Anna and Davidson, Karina W and Hegele, Robert A and Heid, Iris and Hofker, Marten H and Huggins, Gordon S and Illig, Thomas and Johnson, Julie A and Kirkland, Susan and K{\"o}nig, Wolfgang and Langaee, Taimour Y and McCaffery, Jeanne and Melander, Olle and Mitchell, Braxton D and Munroe, Patricia and Murray, Sarah S and Papanicolaou, George and Redline, Susan and Reilly, Muredach and Samani, Nilesh J and Schork, Nicholas J and van der Schouw, Yvonne T and Shimbo, Daichi and Shuldiner, Alan R and Tobin, Martin D and Wijmenga, Cisca and Yusuf, Salim and Hakonarson, Hakon and Lange, Leslie A and Demerath, Ellen W and Fox, Caroline S and North, Kari E and Reiner, Alex P and Keating, Brendan and Taylor, Kira C} } @article {6552, title = {Meta-analysis of loci associated with age at natural menopause in African-American women.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 Jun 15}, pages = {3327-42}, abstract = {

Age at menopause marks the end of a woman{\textquoteright}s reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

}, keywords = {African Americans, Age Factors, Chromosomes, Human, European Continental Ancestry Group, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Menopause, United States}, issn = {1460-2083}, doi = {10.1093/hmg/ddu041}, author = {Chen, Christina T L and Liu, Ching-Ti and Chen, Gary K and Andrews, Jeanette S and Arnold, Alice M and Dreyfus, Jill and Franceschini, Nora and Garcia, Melissa E and Kerr, Kathleen F and Li, Guo and Lohman, Kurt K and Musani, Solomon K and Nalls, Michael A and Raffel, Leslie J and Smith, Jennifer and Ambrosone, Christine B and Bandera, Elisa V and Bernstein, Leslie and Britton, Angela and Brzyski, Robert G and Cappola, Anne and Carlson, Christopher S and Couper, David and Deming, Sandra L and Goodarzi, Mark O and Heiss, Gerardo and John, Esther M and Lu, Xiaoning and Le Marchand, Lo{\"\i}c and Marciante, Kristin and McKnight, Barbara and Millikan, Robert and Nock, Nora L and Olshan, Andrew F and Press, Michael F and Vaiyda, Dhananjay and Woods, Nancy F and Taylor, Herman A and Zhao, Wei and Zheng, Wei and Evans, Michele K and Harris, Tamara B and Henderson, Brian E and Kardia, Sharon L R and Kooperberg, Charles and Liu, Yongmei and Mosley, Thomas H and Psaty, Bruce and Wellons, Melissa and Windham, Beverly G and Zonderman, Alan B and Cupples, L Adrienne and Demerath, Ellen W and Haiman, Christopher and Murabito, Joanne M and Rajkovic, Aleksandar} } @article {7349, title = {DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.}, journal = {Genome Biol}, volume = {17}, year = {2016}, month = {2016 Dec 12}, pages = {255}, abstract = {

BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 {\texttimes} 10(-7)) in the discovery panel of European ancestry and replicated (P < 2.29 {\texttimes} 10(-4)) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16\%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 {\texttimes} 10(-5)), ten (17\%) CpG sites were associated with a nearby genetic variant (P < 2.50 {\texttimes} 10(-3)), and 51 (88\%) were also associated with at least one related cardiometabolic entity (P < 9.58 {\texttimes} 10(-5)). An additive weighted score of replicated CpG sites accounted for up to 6\% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.

CONCLUSION: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.

}, issn = {1474-760X}, doi = {10.1186/s13059-016-1119-5}, author = {Ligthart, Symen and Marzi, Carola and Aslibekyan, Stella and Mendelson, Michael M and Conneely, Karen N and Tanaka, Toshiko and Colicino, Elena and Waite, Lindsay L and Joehanes, Roby and Guan, Weihua and Brody, Jennifer A and Elks, Cathy and Marioni, Riccardo and Jhun, Min A and Agha, Golareh and Bressler, Jan and Ward-Caviness, Cavin K and Chen, Brian H and Huan, Tianxiao and Bakulski, Kelly and Salfati, Elias L and Fiorito, Giovanni and Wahl, Simone and Schramm, Katharina and Sha, Jin and Hernandez, Dena G and Just, Allan C and Smith, Jennifer A and Sotoodehnia, Nona and Pilling, Luke C and Pankow, James S and Tsao, Phil S and Liu, Chunyu and Zhao, Wei and Guarrera, Simonetta and Michopoulos, Vasiliki J and Smith, Alicia K and Peters, Marjolein J and Melzer, David and Vokonas, Pantel and Fornage, Myriam and Prokisch, Holger and Bis, Joshua C and Chu, Audrey Y and Herder, Christian and Grallert, Harald and Yao, Chen and Shah, Sonia and McRae, Allan F and Lin, Honghuang and Horvath, Steve and Fallin, Daniele and Hofman, Albert and Wareham, Nicholas J and Wiggins, Kerri L and Feinberg, Andrew P and Starr, John M and Visscher, Peter M and Murabito, Joanne M and Kardia, Sharon L R and Absher, Devin M and Binder, Elisabeth B and Singleton, Andrew B and Bandinelli, Stefania and Peters, Annette and Waldenberger, Melanie and Matullo, Giuseppe and Schwartz, Joel D and Demerath, Ellen W and Uitterlinden, Andr{\'e} G and van Meurs, Joyce B J and Franco, Oscar H and Chen, Yii-Der Ida and Levy, Daniel and Turner, Stephen T and Deary, Ian J and Ressler, Kerry J and Dupuis, Jos{\'e}e and Ferrucci, Luigi and Ong, Ken K and Assimes, Themistocles L and Boerwinkle, Eric and Koenig, Wolfgang and Arnett, Donna K and Baccarelli, Andrea A and Benjamin, Emelia J and Dehghan, Abbas} } @article {7261, title = {Epigenetic Signatures of Cigarette Smoking.}, journal = {Circ Cardiovasc Genet}, volume = {9}, year = {2016}, month = {2016 Oct}, pages = {436-447}, abstract = {

BACKGROUND: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.

METHODS AND RESULTS: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1{\texttimes}10(-7) (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1{\texttimes}10(-7) (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs.

CONCLUSIONS: Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.116.001506}, author = {Joehanes, Roby and Just, Allan C and Marioni, Riccardo E and Pilling, Luke C and Reynolds, Lindsay M and Mandaviya, Pooja R and Guan, Weihua and Xu, Tao and Elks, Cathy E and Aslibekyan, Stella and Moreno-Macias, Hortensia and Smith, Jennifer A and Brody, Jennifer A and Dhingra, Radhika and Yousefi, Paul and Pankow, James S and Kunze, Sonja and Shah, Sonia H and McRae, Allan F and Lohman, Kurt and Sha, Jin and Absher, Devin M and Ferrucci, Luigi and Zhao, Wei and Demerath, Ellen W and Bressler, Jan and Grove, Megan L and Huan, Tianxiao and Liu, Chunyu and Mendelson, Michael M and Yao, Chen and Kiel, Douglas P and Peters, Annette and Wang-Sattler, Rui and Visscher, Peter M and Wray, Naomi R and Starr, John M and Ding, Jingzhong and Rodriguez, Carlos J and Wareham, Nicholas J and Irvin, Marguerite R and Zhi, Degui and Barrdahl, Myrto and Vineis, Paolo and Ambatipudi, Srikant and Uitterlinden, Andr{\'e} G and Hofman, Albert and Schwartz, Joel and Colicino, Elena and Hou, Lifang and Vokonas, Pantel S and Hernandez, Dena G and Singleton, Andrew B and Bandinelli, Stefania and Turner, Stephen T and Ware, Erin B and Smith, Alicia K and Klengel, Torsten and Binder, Elisabeth B and Psaty, Bruce M and Taylor, Kent D and Gharib, Sina A and Swenson, Brenton R and Liang, Liming and DeMeo, Dawn L and O{\textquoteright}Connor, George T and Herceg, Zdenko and Ressler, Kerry J and Conneely, Karen N and Sotoodehnia, Nona and Kardia, Sharon L R and Melzer, David and Baccarelli, Andrea A and van Meurs, Joyce B J and Romieu, Isabelle and Arnett, Donna K and Ong, Ken K and Liu, Yongmei and Waldenberger, Melanie and Deary, Ian J and Fornage, Myriam and Levy, Daniel and London, Stephanie J} } @article {7568, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 Oct 13}, pages = {910}, abstract = {

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents{\textquoteright} survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Pirastu, Nicola and Kentistou, Katherine A and Fischer, Krista and Hofer, Edith and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Timmers, Paul R H J and Shen, Xia and Gandin, Ilaria and McDaid, Aaron F and Hansen, Thomas Folkmann and Gordon, Scott D and Giulianini, Franco and Boutin, Thibaud S and Abdellaoui, Abdel and Zhao, Wei and Medina-G{\'o}mez, Carolina and Bartz, Traci M and Trompet, Stella and Lange, Leslie A and Raffield, Laura and van der Spek, Ashley and Galesloot, Tessel E and Proitsi, Petroula and Yanek, Lisa R and Bielak, Lawrence F and Payton, Antony and Murgia, Federico and Concas, Maria Pina and Biino, Ginevra and Tajuddin, Salman M and Sepp{\"a}l{\"a}, Ilkka and Amin, Najaf and Boerwinkle, Eric and B{\o}rglum, Anders D and Campbell, Archie and Demerath, Ellen W and Demuth, Ilja and Faul, Jessica D and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Hingorani, Aroon and Hottenga, Jouke-Jan and Hougaard, David M and Hurme, Mikko A and Ikram, M Arfan and Jylh{\"a}, Marja and Kuh, Diana and Ligthart, Lannie and Lill, Christina M and Lindenberger, Ulman and Lumley, Thomas and M{\"a}gi, Reedik and Marques-Vidal, Pedro and Medland, Sarah E and Milani, Lili and Nagy, Reka and Ollier, William E R and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Rivadeneira, Fernando and Ruggiero, Daniela and Saba, Yasaman and Schmidt, Reinhold and Schmidt, Helena and Slagboom, P Eline and Smith, Blair H and Smith, Jennifer A and Sotoodehnia, Nona and Steinhagen-Thiessen, Elisabeth and van Rooij, Frank J A and Verbeek, Andr{\'e} L and Vermeulen, Sita H and Vollenweider, Peter and Wang, Yunpeng and Werge, Thomas and Whitfield, John B and Zonderman, Alan B and Lehtim{\"a}ki, Terho and Evans, Michele K and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Kardia, Sharon L R and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and van Duijn, Cornelia M and Wilson, James G and Jukema, J Wouter and Kiemeney, Lambertus and Uitterlinden, Andr{\'e} G and Franceschini, Nora and North, Kari E and Weir, David R and Metspalu, Andres and Boomsma, Dorret I and Hayward, Caroline and Chasman, Daniel and Martin, Nicholas G and Sattar, Naveed and Campbell, Harry and Esko, T{\~o}nu and Kutalik, Zolt{\'a}n and Wilson, James F} } @article {8446, title = {Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality.}, journal = {Circ Genom Precis Med}, volume = {13}, year = {2020}, month = {2020 Aug}, pages = {e002766}, abstract = {

BACKGROUND: DNA methylation patterns associated with habitual diet have not been well studied.

METHODS: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.

RESULTS: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected <1.6{\texttimes}10). Hypermethylation of cg18181703 () was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (=5.7{\texttimes}10). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR <4.5{\texttimes}10). For example, hypermethylation of cg11250194 () was associated with lower triglyceride concentrations (MR, =1.5{\texttimes}10).and hypermethylation of cg02079413 (; ) was associated with body mass index (corrected MR, =1{\texttimes}10).

CONCLUSIONS: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

}, issn = {2574-8300}, doi = {10.1161/CIRCGEN.119.002766}, author = {Ma, Jiantao and Rebholz, Casey M and Braun, Kim V E and Reynolds, Lindsay M and Aslibekyan, Stella and Xia, Rui and Biligowda, Niranjan G and Huan, Tianxiao and Liu, Chunyu and Mendelson, Michael M and Joehanes, Roby and Hu, Emily A and Vitolins, Mara Z and Wood, Alexis C and Lohman, Kurt and Ochoa-Rosales, Carolina and van Meurs, Joyce and Uitterlinden, Andre and Liu, Yongmei and Elhadad, Mohamed A and Heier, Margit and Waldenberger, Melanie and Peters, Annette and Colicino, Elena and Whitsel, Eric A and Baldassari, Antoine and Gharib, Sina A and Sotoodehnia, Nona and Brody, Jennifer A and Sitlani, Colleen M and Tanaka, Toshiko and Hill, W David and Corley, Janie and Deary, Ian J and Zhang, Yan and Sch{\"o}ttker, Ben and Brenner, Hermann and Walker, Maura E and Ye, Shumao and Nguyen, Steve and Pankow, Jim and Demerath, Ellen W and Zheng, Yinan and Hou, Lifang and Liang, Liming and Lichtenstein, Alice H and Hu, Frank B and Fornage, Myriam and Voortman, Trudy and Levy, Daniel} } @article {8835, title = {Genetic insights into biological mechanisms governing human ovarian ageing.}, journal = {Nature}, volume = {596}, year = {2021}, month = {2021 Aug}, pages = {393-397}, abstract = {

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1\% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

}, issn = {1476-4687}, doi = {10.1038/s41586-021-03779-7}, author = {Ruth, Katherine S and Day, Felix R and Hussain, Jazib and Mart{\'\i}nez-Marchal, Ana and Aiken, Catherine E and Azad, Ajuna and Thompson, Deborah J and Knoblochova, Lucie and Abe, Hironori and Tarry-Adkins, Jane L and Gonzalez, Javier Martin and Fontanillas, Pierre and Claringbould, Annique and Bakker, Olivier B and Sulem, Patrick and Walters, Robin G and Terao, Chikashi and Turon, Sandra and Horikoshi, Momoko and Lin, Kuang and Onland-Moret, N Charlotte and Sankar, Aditya and Hertz, Emil Peter Thrane and Timshel, Pascal N and Shukla, Vallari and Borup, Rehannah and Olsen, Kristina W and Aguilera, Paula and Ferrer-Roda, M{\`o}nica and Huang, Yan and Stankovic, Stasa and Timmers, Paul R H J and Ahearn, Thomas U and Alizadeh, Behrooz Z and Naderi, Elnaz and Andrulis, Irene L and Arnold, Alice M and Aronson, Kristan J and Augustinsson, Annelie and Bandinelli, Stefania and Barbieri, Caterina M and Beaumont, Robin N and Becher, Heiko and Beckmann, Matthias W and Benonisdottir, Stefania and Bergmann, Sven and Bochud, Murielle and Boerwinkle, Eric and Bojesen, Stig E and Bolla, Manjeet K and Boomsma, Dorret I and Bowker, Nicholas and Brody, Jennifer A and Broer, Linda and Buring, Julie E and Campbell, Archie and Campbell, Harry and Castelao, Jose E and Catamo, Eulalia and Chanock, Stephen J and Chenevix-Trench, Georgia and Ciullo, Marina and Corre, Tanguy and Couch, Fergus J and Cox, Angela and Crisponi, Laura and Cross, Simon S and Cucca, Francesco and Czene, Kamila and Smith, George Davey and de Geus, Eco J C N and de Mutsert, Ren{\'e}e and De Vivo, Immaculata and Demerath, Ellen W and Dennis, Joe and Dunning, Alison M and Dwek, Miriam and Eriksson, Mikael and Esko, T{\~o}nu and Fasching, Peter A and Faul, Jessica D and Ferrucci, Luigi and Franceschini, Nora and Frayling, Timothy M and Gago-Dominguez, Manuela and Mezzavilla, Massimo and Garc{\'\i}a-Closas, Montserrat and Gieger, Christian and Giles, Graham G and Grallert, Harald and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Gu{\'e}nel, Pascal and Haiman, Christopher A and H{\r a}kansson, Niclas and Hall, Per and Hayward, Caroline and He, Chunyan and He, Wei and Heiss, Gerardo and H{\o}ffding, Miya K and Hopper, John L and Hottenga, Jouke J and Hu, Frank and Hunter, David and Ikram, Mohammad A and Jackson, Rebecca D and Joaquim, Micaella D R and John, Esther M and Joshi, Peter K and Karasik, David and Kardia, Sharon L R and Kartsonaki, Christiana and Karlsson, Robert and Kitahara, Cari M and Kolcic, Ivana and Kooperberg, Charles and Kraft, Peter and Kurian, Allison W and Kutalik, Zolt{\'a}n and La Bianca, Martina and Lachance, Genevieve and Langenberg, Claudia and Launer, Lenore J and Laven, Joop S E and Lawlor, Deborah A and Le Marchand, Lo{\"\i}c and Li, Jingmei and Lindblom, Annika and Lindstr{\"o}m, Sara and Lindstrom, Tricia and Linet, Martha and Liu, Yongmei and Liu, Simin and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Magnusson, Patrik K E and Mangino, Massimo and Mannermaa, Arto and Marco, Brumat and Marten, Jonathan and Martin, Nicholas G and Mbarek, Hamdi and McKnight, Barbara and Medland, Sarah E and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Metspalu, Andres and Milani, Lili and Milne, Roger L and Montgomery, Grant W and Mook-Kanamori, Dennis O and Mulas, Antonella and Mulligan, Anna M and Murray, Alison and Nalls, Mike A and Newman, Anne and Noordam, Raymond and Nutile, Teresa and Nyholt, Dale R and Olshan, Andrew F and Olsson, H{\r a}kan and Painter, Jodie N and Patel, Alpa V and Pedersen, Nancy L and Perjakova, Natalia and Peters, Annette and Peters, Ulrike and Pharoah, Paul D P and Polasek, Ozren and Porcu, Eleonora and Psaty, Bruce M and Rahman, Iffat and Rennert, Gad and Rennert, Hedy S and Ridker, Paul M and Ring, Susan M and Robino, Antonietta and Rose, Lynda M and Rosendaal, Frits R and Rossouw, Jacques and Rudan, Igor and Rueedi, Rico and Ruggiero, Daniela and Sala, Cinzia F and Saloustros, Emmanouil and Sandler, Dale P and Sanna, Serena and Sawyer, Elinor J and Sarnowski, Chloe and Schlessinger, David and Schmidt, Marjanka K and Schoemaker, Minouk J and Schraut, Katharina E and Scott, Christopher and Shekari, Saleh and Shrikhande, Amruta and Smith, Albert V and Smith, Blair H and Smith, Jennifer A and Sorice, Rossella and Southey, Melissa C and Spector, Tim D and Spinelli, John J and Stampfer, Meir and St{\"o}ckl, Doris and van Meurs, Joyce B J and Strauch, Konstantin and Styrkarsdottir, Unnur and Swerdlow, Anthony J and Tanaka, Toshiko and Teras, Lauren R and Teumer, Alexander and {\TH}orsteinsdottir, Unnur and Timpson, Nicholas J and Toniolo, Daniela and Traglia, Michela and Troester, Melissa A and Truong, Th{\'e}r{\`e}se and Tyrrell, Jessica and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and Vachon, Celine M and Vitart, Veronique and V{\"o}lker, Uwe and Vollenweider, Peter and V{\"o}lzke, Henry and Wang, Qin and Wareham, Nicholas J and Weinberg, Clarice R and Weir, David R and Wilcox, Amber N and van Dijk, Ko Willems and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wolk, Alicja and Wood, Andrew R and Zhao, Wei and Zygmunt, Marek and Chen, Zhengming and Li, Liming and Franke, Lude and Burgess, Stephen and Deelen, Patrick and Pers, Tune H and Gr{\o}ndahl, Marie Louise and Andersen, Claus Yding and Pujol, Anna and Lopez-Contreras, Andres J and Daniel, Jeremy A and Stefansson, Kari and Chang-Claude, Jenny and van der Schouw, Yvonne T and Lunetta, Kathryn L and Chasman, Daniel I and Easton, Douglas F and Visser, Jenny A and Ozanne, Susan E and Namekawa, Satoshi H and Solc, Petr and Murabito, Joanne M and Ong, Ken K and Hoffmann, Eva R and Murray, Anna and Roig, Ignasi and Perry, John R B} }