Acknowledgments

We thank all participants of the Leiden Longevity Study, Rotter- dam Study, Leiden 85-plus study, Netherlands Twin Register, and the Danish 1905 cohort. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Sys- tems Biology, and the Netherlands Consortium for Healthy Age- ing (Grant 050-060-810), all in the framework of the Netherlands Genomics Initiative ⁄Netherlands Organization for Scientific Research (NWO) and by Unilever Colworth.

APOE-independent association of rs2075650 with longevity To determine whether the association of rs2075650 with gevity was independent of the APOE e2⁄e3⁄e4 polymorphism, logistic regression model with adjustment for rs429358, and an interaction term for e2⁄e3 with e3⁄e4 was tested et al., 2009):

The generation and management of GWAS genotype data for the Rotterdam study is supported by the Netherlands Organisation for Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2) and the Netherlands Genomics Initiative (NGI)⁄Nether- lands Organisation for Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam, the Nether- lands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Min- istry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

Status was coded as 0 (control) or 1 (long-lived case), Study was coded as 0 (LLS GWAS), 1 (Leiden 85-plus replication study), or 2 (Danish replication study), and the genotypes of rs2075650, rs429358, and rs7412 were coded as 0 (homozy- gous for the common allele), 1 (heterozygous), or 2 (homozy- gous for the rare allele). STATA⁄SE 11.1 (StataCorp LP, College Station, TX, USA) was used for this analysis.

Prospective analysis

Prospective analysis of rs2075650 and rs429358 was performed with 944 nonagenarian siblings from the LLS, 976 octogenarians and nonagenarians from the Leiden 85-plus study, and 1578 nonagenarians from the Danish 1905 cohort.

The data collection of the Danish 1905 cohort is supported by the US National Institute on Aging, research grant NIA-P01- AG08761, and the Danish Aging Research Center is supported by a grant from the VELUX foundation.

After a mean follow-up time of 5.7 years (LLS), 14.8 years (Leiden 85-plus study), and 11.4 years (Danish 1905 cohort), 73.2% (n = 691) (LLS), 84.8% (n = 828) (Leiden 85-plus study), and 98.9% (n = 1561) (Danish 1905 cohort) of the individuals had died.

The data collection of the Netherlands Twin Register is sup- ported by NWO (904-61-090; 904-61-193; 480-04-004; 400- 05-717; SPI 56-464-14192), Center for Medical Systems Biology (NWO Genomics; Centre for Neurogenomics and Cognitive Research (CNCR-VU); the EU (EU/QLRT-2001-01254); Genome scan for neuroticism (NIMH R01 MH059160); the Geestkracht program of ZonMW (10-000-1002), and institutes involved in NESDA (VU University Medical Center, Leiden University Medical Center, GGZ Buitenamstel-Geestgronden, Rivierduinen, Univer- sity Medical Center Groningen, GGZ Lentis, GGZ Friesland, GGZ Drenthe). The genotyping of the samples was provided through the Genetic Association Information Network (GAIN).

Mortality analyses were performed with STATA⁄SE 11.1 (StataCorp LP) using a sex-adjusted, left-truncated Cox propor- tional hazards model to adjust for late entry into the data set according to age.

Author contributions

Serum parameter = b0 + b1*Age + b2*Sex + b3*(Age*Sex) + b4*Group + b5*rs429358 (Model 2)

Authors contributed as follows JD, MB, BTH, RGJW, PES; Data analysis, drafting manuscript, study design Leiden Lon-

gevity Study H-WU, QH, JJH-D; Statistical data analysis DK, RB, HEDS, NL, EBA, WMP, DH; Data collection and data analysis Leiden Longevity Study MK, LC, HT, AJC, FR, EJdG, DIB, AGU, KC, CMD; Data analysis and data collection GWAS controls and replication cohorts MP; DNA isolations Leiden Longevity Study FJO, DAG; Data collection Leiden Longevity Study GWAS cases.

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