ja, die Studie ist auf Englisch. Vielleicht \u00fcbersetzenh wir sie demn\u00e4chst. Bitte sehr:
Human Genetics (2005) Online:
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\nDOI: 10.1007\/s00439-004-1241-4
\n
\nThe original publication is available at:
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\nhttp:\/\/springerlink.metapress.com\/openurl.asp?genre=article&id=doi:10.1007\/s00439-
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\n004-1241-4
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\nOriginal Investigation
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\nA genomewide scan of male sexual orientation
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\nBrian S. Mustanski1, 2, Michael G. DuPree1, 3, Caroline M. Nievergelt4,
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\nSven Bocklandt1, 5, Nicholas J. Schork4 and Dean H. Hamer1
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\n(1) Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health,
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\nBethesda, Md., USA
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\n(2) Institute for Juvenile Research Department of Psychiatry, University of Illinois at
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\nChicago (M\/C 747), 1747 W. Roosevelt Road, Chicago, IL 60608, USA
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\n(3) Department of Anthropology, Pennsylvania State University, University Park, Pa.,
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\nUSA
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\n(4) Department of Psychiatry, University of California, San Diego, Calif., USA
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\n(5) Department of Human Genetics, David Geffen School of Medicine at UCLA, Los
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\nAngeles, Calif., USA
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\nBrian S. Mustanski
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\nEmail: bmustanski@psych.uic.edu
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\nPhone: +1-312-9969505
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\nReceived: 16 September 2004 Accepted: 30 November 2004 Published online:
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\n12 January 2005
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\nAbstract This is the first report of a full genome scan of sexual orientation in men. A
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\nsample of 456 individuals from 146 families with two or more gay brothers was
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\ngenotyped with 403 microsatellite markers at 10-cM intervals. Given that previously
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\nreported evidence of maternal loading of transmission of sexual orientation could indicate
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\nepigenetic factors acting on autosomal genes, maximum likelihood estimations (mlod)
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\nscores were calculated separated for maternal, paternal, and combined transmission. The
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\nhighest mlod score was 3.45 at a position near D7S798 in 7q36 with approximately
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\nequivalent maternal and paternal contributions. The second highest mlod score of 1.96
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\nwas located near D8S505 in 8p12, again with equal maternal and paternal contributions.
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\nA maternal origin effect was found near marker D10S217 in 10q26, with a mlod score of
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\n1.81 for maternal meioses and no paternal contribution. We did not find linkage to Xq28
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\nin the full sample, but given the previously reported evidence of linkage in this region,
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\nwe conducted supplemental analyses to clarify these findings. First, we re-analyzed our
\n
\npreviously reported data and found a mlod of 6.47. We then re-analyzed our current data,
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\nafter limiting the sample to those families previously reported, and found a mlod of 1.99.
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\nThese Xq28 findings are discussed in detail. The results of this first genome screen for
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\nnormal variation in the behavioral trait of sexual orientation in males should encourage
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\nefforts to replicate these findings in new samples with denser linkage maps in the
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\nsuggested regions.
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\nBrian S. Mustanski and Michael G. DuPree contributed equally to this work.
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\nIntroduction
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\nAlthough most males report primarily heterosexual attractions, a significant minority
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\n(approximately 2%\u20136%) of males report predominantly homosexual attractions
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\n(Diamond 1993; Laumann et al. 1994; Wellings et al. 1994). Multiple lines of evidence
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\nsuggest that biological factors play a role in explaining individual differences in male
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\nsexual orientation (MIM 306995). For example, the third interstitial nuclei of the human
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\nanterior hypothalamus (INAH3), which is significantly smaller in females, is also
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\nreported to be smaller in homosexual males (LeVay 1991). Byne and colleagues (2001)
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\nfollowed up on this finding by reporting a trend for INAH3 to occupy a smaller volume
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\nin homosexual men than in heterosexual men, with no significant difference in the
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\nnumber of neurons within the nucleus. Neuropsychological studies have reported
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\ndifferences in performance with respect to tasks that show sex differences, such as spatial
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\nprocessing (e.g., Rahman and Wilson 2003), which may indicate differences in relevant
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\nneural correlates (e.g., parietal cortex). The strong link between adult sexual orientation
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\nand childhood gender-related traits expressed at an early age (Bailey and Zucker 1995)
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\nsuggests that such biological influences act early in development, possibly prenatally.
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\nSimilarly, the correlation between sexual orientation and a variety of prenatally canalized
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\nanthropometric traits suggests that sexual orientation differentiation probably occurs
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\nbefore birth (for a review, see Mustanski et al. 2002). Despite this evidence, specific
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\nneurodevelopmental pathways have yet to be elucidated.
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\nFamily and twin studies have provided evidence for a genetic component to male sexual
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\norientation. Family studies, using a variety of ascertainment strategies, document an
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\nelevation in the rate of homosexuality among relatives of homosexual probands (for a
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\nreview, see Bailey and Pillard 1995). Several family studies report evidence of increased
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\nmaternal transmission of male homosexuality (Hamer et al. 1993; Rice et al. 1999a),
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\nwhereas others find no increase relative to paternal transmission (Bailey et al. 1999;
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\nMcKnight and Malcolm 2000). Twin studies consistently show that male sexual
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\norientation is moderately heritable (for a review, see Mustanski et al. 2002). For example,
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\ntwo recent twin studies in population-based samples both report moderate heritability
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\nestimates, with the remaining variance being explained by nonshared environmental
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\ninfluences (Kendler et al. 2000; Kirk et al. 2000). The results from family and twin
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\nstudies demonstrate that sexual orientation is a complex (i.e., does not show simple
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\nMedelian inheritance) and multifactorial phenotype.
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\nA more limited number of studies have attempted to map specific genes contributing to
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\nvariation in sexual orientation. Given the evidence for increased maternal transmission,
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\ninitial efforts focused on the X chromosome. One study produced evidence of significant
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\nlinkage, based on Lander and Kruglyak (1995) criteria, to markers on Xq28 (Hamer et al.
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\n1993). Another study, from the same laboratory but with a new sample, reported a
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\nsignificant replication of these findings (Hu et al. 1995). An independent group produced
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\ninconclusive results regarding linkage to Xq28 (discussed in Sanders and Dawood 2003)
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\nbut did not publish the findings in a peer-reviewed journal. All three of these studies
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\nexcluded families showing evidence for non-maternal transmission. A fourth study from
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\nanother independent group found no support for linkage, even when excluding cases with
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\nsuggestive father-to-son transmission (Rice et al. 1999b). An analysis of the results across
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\nall four studies produced a statistically suggestive multiple scan probability (MSP) value
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\nof 0.00003 (Sanders and Dawood 2003). Two candidate gene studies have been
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\nconducted, both producing null results: one for the androgen receptor (AR; Macke et al.
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\n1993) and another for aromatase (CYP19A1; Dupree et al. 2004), on Xq12 and 15q21.2,
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\nrespectively.
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\nGiven the complexity of sexual orientation, numerous genes are likely to be involved,
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\nmany of which are expected to be autosomal rather than sex-linked. Indeed, the modest
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\nlevels of linkage that have been reported for the X chromosome can account for, at most,
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\nonly a fraction of the overall heritability of male sexual orientation as deduced from twin
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\nstudies. Therefore, we have undertaken a genomewide linkage scan to aid in the
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\nidentification of genes contributing to variation in sexual orientation. As in previous
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\nstudies, we diminished the probability of false positives (i.e., gay men who identify as
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\nheterosexual) by only studying self-identified gay men. Unlike previous studies that have
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\nfocused solely on the X-chromosome and thus excluded families showing evidence of
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\nnon-maternal transmission, this study did not use transmission pattern as an exclusion
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\ncriteria. To consider the possibility that previously reported evidence of maternal loading
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\nof transmission of sexual orientation was attributable to epigenetic factors acting on
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\nautosomal genes, we calculated maximum likelihood estimations (mlod) scores separated
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\nby maternal or paternal transmission and the combined statistic. Based on Lander and
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\nKruglyak s (1995) criteria, we found one region of near significance and two regions
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\nclose to the criteria for suggestive linkage.
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\nMaterials and methods
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\nFamily ascertainment and assessment
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\nThe sample consisted of a total of 456 individuals from 146 unrelated families, of which
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\n137 families had two gay brothers and 9 families had three gay brothers. Thirty of the
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\nfamilies included one parent, and 30 of the families included both parents. Additionally,
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\n46 of the families included at least one heterosexual male or female full sibling (up to 6
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\nadditional siblings per family). The sample included 40 families previously reported by
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\nHamer et al. (1993), 33 families previously reported by Hu et al. (1995), and 73
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\npreviously unreported families. The 73 previously described families were selected for
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\nthe presence of two gay brothers with no indication of non-maternal transmission by the
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\ncriteria described previously (Hamer et al. 1993; Hu et al. 1995). For the 73 new families,
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\nthe sole inclusion criterion was the presence of at least two self-acknowledged gay male
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\nsiblings.
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\nSubjects were recruited through advertisements in local and national homophile
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\npublications as described elsewhere (Hamer et al. 1993; Hu et al. 1995). The participants
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\nwere predominantly white (94.5%), college educated (87.4%), and of middle to upper
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\nsocioeconomic status. The mean (SD) age for the gay siblings was 36.98 (8.64). The
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\nprotocol was approved by the NCI Institutional Review Board, and each participant
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\nsigned an informed consent form prior to interview, questionnaire completion, and the
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\ndonation of blood for DNA extraction.
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\nSexual orientation was assessed through a structured interview or a questionnaire that
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\nincluded a sexual history and the Kinsey scales of sexual attraction, fantasy, behavior,
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\nand self-identification (Kinsey et al. 1948). Each scale ranges from 0 (exclusively
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\nheterosexual) to 6 (exclusively homosexual). The mean (SD) of these four scales for the
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\ngay males in this study was 5.65 (0.46)
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\nGenotyping
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\nDNA was extracted from peripheral blood by a commercial service (Genetic Design,
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\nGreensboro, N.C., USA). A multiplex polymerase chain reaction (PCR) was conducted as
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\ndescribed (Dupree et al. 2004), with 403 microsatellite markers from the ABI PRISM
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\nLinkage Mapping Set Version 2.5 with an average resolution of 10 cM. Following the
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\nmanufacturer s guidelines, products were analyzed on an ABI Prism 310 or 3100 and
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\nsized with the GeneScan version 3.1.2 program (PE Biosystems, Foster City, Calif.,
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\nUSA), and genotypes were assigned with the Genotyper version 3.6 program (PE
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\nBiosystems). A PCR product from a DNA reference sample (CEPH 1347-02) was used to
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\nmonitor sizing conformity (PE Biosystems). Across the 403 markers, genotypes were
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\nascertained on average for 95% of the 456 individuals. Mendelian incompatibilities
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\n(<0.05% of genotypes) were removed from the data prior to analyses by using the\n
\nsib_clean routine from ASPEX version 2.4 (Hinds and Risch 1996). The computer
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\nprogram CERVUS 2.0 (Marshall et al. 1998) was employed to test for deviation from the
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\nHardy-Weinberg equilibrium (HW) and to calculate polymorphism information contents
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\n(PICs) at all loci. We found that the markers had a mean (SD) PIC of 0.76 (0.08), and
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\n1.31% of the markers deviated significantly from HW.
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\nStatistical analyses
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\nNonparametric exclusion mapping of affected sib-pair data (ASP) was performed by
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\nusing ASPEX version 2.4 (Hinds and Risch 1996). ASPEX calculates the percentage of
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\nidentical by descent (%IBD) sharing and reports the proportion of shared alleles of
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\npaternal, maternal, and combined origin. The results for alleles of combined origin also
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\ninclude alleles where the parental origin is unknown. We calculated mlod with a linear
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\nmodel and assuming a multiplicative model. The ASPEX SIB_PHASE algorithm was
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\napplied; this uses allele frequency information to reconstruct and to phase missing
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\nparental information. Sex-specific recombination maps were used for the calculation of
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\nmultipoint mlod scores. Marker order and map positions were determined by using an
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\nintegrated map (Nievergelt et al. 2004) based on the deCODE genetic map and updated
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\nphysical map information.
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\nResults
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\nResults from the multipoint analyses on chromosomes 1 through 22 are shown in Fig. 1
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\nfor paternal, maternal, and combined meioses. Our complete genome scan for male
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\nsexual orientation yielded three interesting peaks with mlod scores greater than 1.8,
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\nlocated on chromosomes 7, 8, and 10. Table 1 contains additional information concerning
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\nthese peaks, including the nearest marker, the location, MLOD, and allele sharing.
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\nAdditionally, Table 1 contains the approximate boundary of the linkage peak, by
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\nreporting the approximate cM position at which the mlod score declines below 1.0. For
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\nchromosomes 7 and 8, the peak is a result of approximately equal contributions from
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\nmaternal and paternal transmission, whereas a maternal-origin effect was found for the
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\npeak on chromosome 10.
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\nFig. 1 Genome scan results. The x-axis is the chromosome location (cM), and the y-axis
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\nis the mlod score. Graphics included for combined (a), maternal (b), and paternal (c)
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\nmeioses
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\nTable 1 Chromosomal locations with nominally significant linkage peaks. The cM
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\npositions in parentheses indicate the boundary at which the mlod score declines below
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\n1.0. For chromosomes 7 and 8, the position is based on the combined map, but for
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\nchromosome 10, the position is based on the female map.
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\nLocation mlod Nearby
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\nmarker cM Cyto Paternal Maternal Combined
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\nPercentage of
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\nsharing
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\nD7S798 169.9 (155.1\u2013
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\nend) 7q36 2.05 2.26 3.45 62.59
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\nD8S505 54.2 (45.1\u2013
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\n64.8) 8p12 1.38 0.93 1.96 60.10
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\nD10S217 208.1 (201.8\u2013
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\n217.4) 10q26 \u20130.13 1.89 1.43 58.51
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\nFigure 2 shows the multipoint mlod plots for the X chromosome. Analyses of the full
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\nsample (dashed line) did not produce any chromosomal regions with mlod scores greater
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\nthan 1.0. Given the previous evidence of linkage to Xq28 with a portion of the sample
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\nreported here (Hamer et al. 1993; Hu et al. 1995), we performed supplemental analyses to
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\ndetermine why we did not find linkage in the full sample. We began by re-analyzing the
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\ndata from the previously reported 73 families, which had been selected for showing no
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\nevidence of paternal transmission, by using updated marker positions (dotted line). This
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\nproduced a maximum mlod score of 6.47 for markers in the Xq28 region. We then
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\nperformed a linkage analysis, with only the markers from the ABI linkage mapping set,
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\non these same 73 families. This produced a maximum mlod score of 1.99 for markers in
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\nthe Xq28 region. Although the mlod score is higher when using the current markers in the
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\nlimited sample compared with the full sample (1.99 vs. 0.35), it is still significantly lower
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\nthan the previously reported markers in the limited sample. We provide Table 2 in order
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\nto help clarify these results. Table 2 provides singlepoint and multipoint results for the 73
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\npreviously reported families on all markers ever reported from our group, starting with
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\nthe most telemeric new Xq28 marker. Table 2 makes it clear that, although the multipoint
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\nresults suggest a dramatic change in mlod score between the current markers and the
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\npreviously reported markers (6.47 vs. 1.99 for markers 0.62 cM apart), the singlepoint
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\nresults are not dramatically different (2.23 vs. 1.47). This difference is likely to be
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\nattributable to two factors. First, the previous reports focused on the X chromosome and
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\ncontained many more markers in the Xq28 region; the previously reported markers had
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\nan average resolution of 1 marker every 1.12 cM, whereas the current markers had an
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\naverage resolution 6.97 cM in the Xq28 region. The higher concentration of previously
\n
\nreported markers surely allowed for the extraction of more multipoint linkage
\n
\ninformation. Second, there were more telomeric markers in the previously reported
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\nmapping sets than in the current one. The singlepoint results showed a trend for higher
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\nmlod scores closer to the telomere, with the exception of JXYQ28, which had a low PIC
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\n(0.28).
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\nFig. 2 Multipoint linkage analysis for the X chromosome. The x-axis is the chromosome
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\nlocation (cM), and the y-axis is the mlod score. \u2014\u2014 Current markers with sample
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\nrestricted to previously reported families. – – – – Current markers with full sample. ……
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\nPreviously reported markers with previously reported families
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\nTable 2 Supplemental analyses comparing Xq28 results across markers reported on in
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\n1995, 1997, and the current report. All analyses reported here are based on the sample
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\nrestricted to those families previously reported. Current markers and previously reported
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\nmarkers were analyzed separately for the purpose of calculating multipoint mlod scores.
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\nMarker Study
\n
\nyear
\n
\nLocation
\n
\n(cM)
\n
\nMarker
\n
\ndistance
\n
\n(cM)
\n
\nMultipoint
\n
\nmlod
\n
\n(previous
\n
\nmarkers)
\n
\nMultipoint
\n
\nmlod (current
\n
\nmarkers)
\n
\nSinglepoint
\n
\nmlod
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\nDXS1073 Current 188.22 1.99 1.47
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\nF8C 1993 188.84 0.62 6.47 2.23
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\nDXS1108 1993 190.32 1.47 6.27 4.22
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\nJXYQ28 1995 190.47 0.15 6.28 0.48
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\nDXYS154 1993 190.79 0.32 5.71 3.53
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\nDiscussion
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\nThis study reports results from the first full genome scan for male sexual orientation.
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\nUsing 73 previously reported families and 73 new families with two or more gay male
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\nsiblings, we found three new regions of genetic interest. Our strongest finding was on
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\n7q36 with a combined mlod score of 3.45 and equal contribution from maternal and
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\npaternal allele transmission. This score falls just short of Lander and Kruglyak s (1995)
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\ncriteria for genomewide significance. Several interesting candidate genes map to this
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\nregion of chromosome 7. Vasoactive intestinal peptide (VIP) receptor type 2 (VIPR2;
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\nMIM 601970) is a G protein-coupled receptor that activates adenylate cyclase in response
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\nto VIP (Metwali et al. 1996), which functions as a neurotransmitter and as a
\n
\nneuroendocrine hormone. VIPR2 is essential for the development of the hypothalamic
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\nsuprachiasmatic nucleus in mice (Harmar et al. 2002), which makes it an interesting
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\ncandidate gene for sexual orientation in view of earlier reports of an enlarged
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\nsuprachiasmatic nucleus in homosexual men (Swaab and Hofman 1990). Sonic hedgehog
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\n(SHH; MIM 600725) plays an essential role in patterning the early embryo, including
\n
\nhemisphere separation (Roessler et al. 1996) and left to right asymmetry (Tsukui et al.
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\n1999). Homosexual men and women show a significant increase in non-righthandedness,
\n
\nwhich is related to brain asymmetry (Lalumiere et al. 2000).
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\nTwo additional regions approached the criteria for suggestive linkage. The region near
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\n8p12 contains several interesting candidate genes, given the hypothesized relationship
\n
\nbetween prenatal hormones and sexual orientation (Mustanski et al. 2002). Gonadotropinreleasing
\n
\nhormone 1 (GNRH1; MIM 152760) stimulates both the synthesis and release of
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\nluteinizing hormone and follicle-stimulating hormone, which are important regulators of
\n
\nsteroidogenesis in the gonads, and inhibits the release of prolactin (Adelman et al. 1986).
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\nGnRH is synthesized in the arcuate nucleus and other nuclei of the hypothalamus
\n
\n(Kawakami et al. 1975). Steroidogenic acute regulatory protein (STAR; MIM 600617)
\n
\nmediates pregnenolone synthesis and is involved in the hypothalamic-pituitary regulation
\n
\nof adrenal steroid production (Sugawara et al. 1995), which in turn plays an important
\n
\nrole in sexual development. Neuregulin1 (NRG1; MIM 142445) produces a variety of
\n
\nisoforms that regulate the growth and differentiation of neuronal and glial cells through
\n
\ninteraction with ERBB receptors (Burden and Yarden 1997; Wen et al. 1994).
\n
\nThe 10q26 region is of special interest because it results from excess sharing of maternal
\n
\nbut not paternal alleles. Previous studies have suggested that there is an excess of
\n
\nhomosexual family members related to the proband through the mother, and we have
\n
\nproposed previously that this might result in part from genomic imprinting (Bocklandt
\n
\nand Hamer 2003). In support of a connection between 10q26 and imprinting, a germline
\n
\ndifferentially methylated region has been identified at this location by Strichman-
\n
\nAlmashanu et al. (2002) who performed a genomewide screen for normally methylated
\n
\nCpG islands and found 12 regions to be differentially methylated in uniparental tissues of
\n
\ngermline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian
\n
\nteratomas (maternal origin). Such CpG islands can regulate the expression of imprinted
\n
\ngenes over distances of several hundred kilobases. The region around the 10q26 CpG
\n
\nislands includes the brain-expressed gene Shadow of Prion Protein (SPRN), several
\n
\ntranscription regulators (ZNF511, VENTX2; MIM 607158), neurotransmitter interacting
\n
\nproteins (DRD1IP; MIM 604647), and cell signaling pathway proteins (INPP5A; MIM
\n
\n600106, GPR123).
\n
\nFour previous linkage studies have been conducted on the X chromosome and together
\n
\nproduce a statistically suggestive MSP in the Xq28 region (Sanders and Dawood 2003).
\n
\nBecause the focus of this study was a full genome scan with the ABI linkage mapping set
\n
\non a partially new set of families, we began by reporting results for these markers on the
\n
\nfull sample. This analysis did not produce evidence of linkage in the Xq28 region;
\n
\ntherefore, we conducted supplemental analyses to clarify this result given previous
\n
\nfindings. Our first supplemental analysis combined results from the two previous reports
\n
\nfrom our group (Hamer et al. 1993; Hu et al. 1995) in order to determine the magnitude
\n
\nof the linkage signal in the 73 previously reported families that currently comprised half
\n
\nof the current sample. This produced a mlod of 6.47. To determine whether the lack of
\n
\nlinkage evidence in the full sample was attributable to the new markers or the additional
\n
\nfamilies (who were not selected based on family transmission patterns), we then
\n
\nconducted analyses on the previously reported families by using the markers from the
\n
\nABI linkage mapping set. This produced an mlod score of 1.99. Table 2, which provides
\n
\na summary of the single point and multipoint results for this comparison, suggests that
\n
\nthat the difference in mlod score between the restricted sample with the old and new
\n
\nmarkers is attributable to the non-optimal position and density of the new markers. The
\n
\ndifference in mlod scores between the full sample and the sample restricted to families
\n
\nwithout evidence of paternal transmission (with the goal of enriching the sample for
\n
\nfamilies showing maternal transmission) denotes the possibility of etiologic heterogeneity
\n
\nfor the proposed Xq28 locus.
\n
\nSeveral limitations of the current study should be noted. First, we were unable to
\n
\ncalculate empirically derived significance levels for this project because none of the
\n
\nsimulation programs that currently exist allow for the use of sex-specific maps with ASP
\n
\ndata. Future development of simulation programs that allow for the incorporation of this
\n
\nimportant information will prevent this limitation in the future. Second, our marker set
\n
\nhad an average resolution of 10 cM, which may have led to underestimated mlod scores.
\n
\nWe discuss in detail above the likely negative effects that this had on our X chromosome
\n
\nresults. Optimally, genome scans are followed up with dense markers placed in promising
\n
\nregions, but because of financial limitations, we were unable to do this. Future studies
\n
\nwill undoubtedly employ more sophisticated and dense marker sets. Third, we analyzed
\n
\nonly 146 independent families, which is a small sample for a complex trait such as sexual
\n
\norientation. Approximately half of these families have previously been included in
\n
\nreports on the X chromosome (Hamer et al. 1993; Hu et al. 1995). Future research should
\n
\nbe conducted on a new and larger sample of participants. Our linkage results should be
\n
\ninterpreted with consideration of the fact that we only included families with two selfidentified
\n
\ngay brothers. Our results may not extrapolate to individuals who do not meet
\n
\nour exclusion criteria, such as individuals who engage in same-sex behavior but do not
\n
\nidentify as gay or individuals who identify as bisexual. The definition of homosexuality is
\n
\ncomplicated, and future genetic research would benefit from additional phenotype
\n
\ndevelopment or the identification of endophenotypes for sexual orientation (Mustanski et
\n
\nal. 2002). The identification of basic processes that underlie sexual orientation could
\n
\nincrease the power of future genetic studies. A related limitation is that we did not
\n
\ninclude females in our study because it is not yet clear if female sexual orientation is
\n
\ndetermined by the same factors as male sexual orientation (for a discussion, see
\n
\nMustanski et al. 2002). Future research with mix-sexed samples should help to answer
\n
\nthis question. Finally, we did not collect data on the number of older brothers, which
\n
\nshows a robust association with male sexual orientation (Blanchard 2004). Future studies
\n
\nshould collect this data to allow for explorations of gene by environment interactions; this
\n
\ncould increase the ability to identify genetic loci and also help to elucidate the process
\n
\nlinking number of older brothers to sexual orientation.
\n
\nIn summary, we report the first genome scan for loci involved in the complex phenotype
\n
\nof male sexual orientation. We have also identified several chromosomal regions and
\n
\ncandidate genes for future exploration. The molecular analysis of genes involved in
\n
\nsexual orientation could greatly advance our understanding of human variation,
\n
\nevolution, and brain development. In the absence of obvious animal models, genetic
\n
\nlinkage and association studies provide the best opportunity for discovering these loci.
\n
\nAcknowledgements We thank all the individuals who participated in the project for
\n
\ntheir time and openness and Lynn Goldin and Danielle Dick for comments on the
\n
\nmanuscript. B.S.M. was supported by a NSF Graduate Research Fellowship and an NIH
\n
\nSummer Research Fellowship. N.J.S. and C.M.N. were supported in part by the NHLBI
\n
\nFamily Blood Pressure Program (FBPP; HL64777-01).
\n
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ja, die Studie ist auf Englisch. Vielleicht \u00fcbersetzenh wir sie demn\u00e4chst. Bitte sehr: <\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[12],"tags":[],"class_list":["post-83568","post","type-post","status-publish","format-standard","hentry","category-femleben","entry"],"yoast_head":"\n